An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.
An autosomal dominant vascular anomaly characterized by telangiectases of the skin and mucous membranes and by recurrent gastrointestinal bleeding. This disorder is caused by mutations of a gene (on chromosome 9q3) which encodes endoglin, a membrane glycoprotein that binds TRANSFORMING GROWTH FACTOR BETA.
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A group of rare, idiopathic, congenital retinal vascular anomalies affecting the retinal capillaries. It is characterized by dilation and tortuosity of retinal vessels and formation of multiple aneurysms, with different degrees of leakage and exudates emanating from the blood vessels.
An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Impairment of the ability to coordinate the movements required for normal ambulation (WALKING) which may result from impairments of motor function or sensory feedback. This condition may be associated with BRAIN DISEASES (including CEREBELLAR DISEASES and BASAL GANGLIA DISEASES); SPINAL CORD DISEASES; or PERIPHERAL NERVOUS SYSTEM DISEASES.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Bleeding from the nose.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Keto-pyrans.
One of the two types of ACTIVIN RECEPTORS. They are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES. The major type II activin receptors are ActR-IIA and ActR-IIB.
Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the CAPILLARIES. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas.
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.
Complex cytotoxic antibiotic obtained from Streptomyces flocculus or S. rufochronmogenus. It is used in advanced carcinoma and causes leukopenia.
A mild form of LIMITED SCLERODERMA, a multi-system disorder. Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.
Established cell cultures that have the potential to propagate indefinitely.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
The process by which a DNA molecule is duplicated.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
An individual having different alleles at one or more loci regarding a specific character.
Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
Compounds that inhibit cell production of DNA or RNA.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
A cell line derived from cultured tumor cells.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Proteins that specifically bind to IRON.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A state of elevated cardiac output due to conditions of either increased hemodynamic demand or reduced cardiac oxygen output. These conditions may include ANEMIA; ARTERIOVENOUS FISTULA; THYROTOXICOSIS; PREGNANCY; EXERCISE; FEVER; and ANOXIA. In time, compensatory changes of the heart can lead to pathological form of high cardiac output and eventual HEART FAILURE.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
One of the two types of ACTIVIN RECEPTORS or activin receptor-like kinases (ALK'S). There are several type I activin receptors. The major active ones are ALK-2 (ActR-IA) and ALK-4 (ActR-IB).
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)
An individual in which both alleles at a given locus are identical.
A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.
A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.
Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A characteristic symptom complex.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Biochemical identification of mutational changes in a nucleotide sequence.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Human COLORECTAL CARCINOMA cell line.
An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A general term for various neoplastic diseases of the lymphoid tissue.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.
Acquired degenerative dilation or expansion (ectasia) of normal BLOOD VESSELS, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the GASTROINTESTINAL TRACT leading to GASTROINTESTINAL HEMORRHAGE and ANEMIA.
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Mapping of the KARYOTYPE of a cell.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.
Congenital vascular anomalies in the brain characterized by direct communication between an artery and a vein without passing through the CAPILLARIES. The locations and size of the shunts determine the symptoms including HEADACHES; SEIZURES; STROKE; INTRACRANIAL HEMORRHAGES; mass effect; and vascular steal effect.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. (1/586)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.  (+info)

Ataxia, ocular telangiectasia, chromosome instability, and Langerhans cell histiocytosis in a patient with an unknown breakage syndrome. (2/586)

An 8 year old boy who had Langerhans cell histiocytosis when he was 15 months old showed psychomotor regression from the age of 2 years. Microcephaly, severe growth deficiency, and ocular telangiectasia were also evident. Magnetic nuclear resonance imaging showed cerebellar atrophy. Alphafetoprotein was increased. Chromosome instability after x irradiation and rearrangements involving chromosome 7 were found. Molecular study failed to show mutations involving the ataxia-telangiectasia gene. This patient has a clinical picture which is difficult to relate to a known breakage syndrome. Also, the relationship between the clinical phenotype and histiocytosis is unclear.  (+info)

Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. (3/586)

Replication protein A (RPA) is a DNA single-strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated. This response appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA-PK activation and RPA2 phosphorylation. DNA-PK activation and RPA2 phosphorylation were prevented by the cell-cycle checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase-DNA cleavage complex could lead to a juxtaposition of replication fork-associated RPA and DNA double-strand end-associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S-phase checkpoint mechanism. KEYWORDS: camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation  (+info)

Requirement of ATM in phosphorylation of the human p53 protein at serine 15 following DNA double-strand breaks. (4/586)

Microinjection of the restriction endonuclease HaeIII, which causes DNA double-strand breaks with blunt ends, induces nuclear accumulation of p53 protein in normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this induction of p53 accumulation is not observed in ataxia telangiectasia (AT) fibroblasts. HaeIII-induced p53 protein in normal fibroblasts is phosphorylated at serine 15, as determined by immunostaining with an antibody specific for phosphorylated serine 15 of p53. This phosphorylation correlates well with p53 accumulation. Treatment with lactacystin (an inhibitor of the proteasome) or heat shock leads to similar levels of p53 accumulation in normal and AT fibroblasts, but the p53 protein lacks a phosphorylated serine 15. Following microinjection of HaeIII into lactacystin-treated normal fibroblasts, lactacystin-induced p53 protein is phosphorylated at serine 15 and stabilized even in the presence of cycloheximide. However, neither stabilization nor phosphorylation at serine 15 is observed in AT fibroblasts under the same conditions. These results indicate the significance of serine 15 phosphorylation for p53 stabilization after DNA double-strand breaks and an absolute requirement for ATM in this phosphorylation process.  (+info)

Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia. (5/586)

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69-9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18-2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought.  (+info)

Abnormal myo-inositol and phospholipid metabolism in cultured fibroblasts from patients with ataxia telangiectasia. (6/586)

Ataxia telangiectasia (AT) is a complex autosomal recessive disorder that has been associated with a wide range of physiological defects including an increased sensitivity to ionizing radiation and abnormal checkpoints in the cell cycle. The mutated gene product, ATM, has a domain possessing homology to phosphatidylinositol-3-kinase and has been shown to possess protein kinase activity. In this study, we have investigated how AT affects myo-inositol metabolism and phospholipid synthesis using cultured human fibroblasts. In six fibroblast lines from patients with AT, myo-inositol accumulation over a 3-h period was decreased compared to normal fibroblasts. The uptake and incorporation of myo-inositol into phosphoinositides over a 24-h period, as well as the free myo-inositol content was also lower in some but not all of the AT fibroblast lines. A consistent finding was that the proportion of 32P in total labeled phospholipid that was incorporated into phosphatidylglycerol was greater in AT than normal fibroblasts, whereas the fraction of radioactivity in phosphatidic acid was decreased. Turnover studies revealed that AT cells exhibit a less active phospholipid metabolism as compared to normal cells. In summary, these studies demonstrate that two manifestations of the AT defect are alterations in myo-inositol metabolism and phospholipid synthesis. These abnormalities could have an effect on cellular signaling pathways and membrane production, as well as on the sensitivity of the cells to ionizing radiation and proliferative responses.  (+info)

Cell cycle control, checkpoint mechanisms, and genotoxic stress. (7/586)

The ability of cells to maintain genomic integrity is vital for cell survival and proliferation. Lack of fidelity in DNA replication and maintenance can result in deleterious mutations leading to cell death or, in multicellular organisms, cancer. The purpose of this review is to discuss the known signal transduction pathways that regulate cell cycle progression and the mechanisms cells employ to insure DNA stability in the face of genotoxic stress. In particular, we focus on mammalian cell cycle checkpoint functions, their role in maintaining DNA stability during the cell cycle following exposure to genotoxic agents, and the gene products that act in checkpoint function signal transduction cascades. Key transitions in the cell cycle are regulated by the activities of various protein kinase complexes composed of cyclin and cyclin-dependent kinase (Cdk) molecules. Surveillance control mechanisms that check to ensure proper completion of early events and cellular integrity before initiation of subsequent events in cell cycle progression are referred to as cell cycle checkpoints and can generate a transient delay that provides the cell more time to repair damage before progressing to the next phase of the cycle. A variety of cellular responses are elicited that function in checkpoint signaling to inhibit cyclin/Cdk activities. These responses include the p53-dependent and p53-independent induction of Cdk inhibitors and the p53-independent inhibitory phosphorylation of Cdk molecules themselves. Eliciting proper G1, S, and G2 checkpoint responses to double-strand DNA breaks requires the function of the Ataxia telangiectasia mutated gene product. Several human heritable cancer-prone syndromes known to alter DNA stability have been found to have defects in checkpoint surveillance pathways. Exposures to several common sources of genotoxic stress, including oxidative stress, ionizing radiation, UV radiation, and the genotoxic compound benzo[a]pyrene, elicit cell cycle checkpoint responses that show both similarities and differences in their molecular signaling.  (+info)

Rapid and efficient ATM mutation detection by fluorescent chemical cleavage of mismatch: identification of four novel mutations. (8/586)

Mutations in the Ataxia Telangiectasia Mutated (ATM) gene are responsible for the autosomal recessive disease Ataxia Telangiectasia (A-T). A wide variety of mutations scattered across the entire coding region (9168bp) of ATM have been found, which presents a challenge in developing an efficient mutation screening strategy for detecting unknown mutations. Fluorescent chemical cleavage of mismatch (FCCM) is an ideal mutation screening method, offering a non-radioactive alternative to other techniques such as restriction endonuclease fingerprinting (REF). Using FCCM, we have developed an efficient, accurate and sensitive mutation detection method for screening RT-PCR products for ATM mutations. We have identified seven ATM mutations in five A-T families, four of which are previously unknown. We quantified ATM protein expression in four of the families and found variable ATM protein expression (0-6.4%), further evidence for mutant ATM protein expression in both classic and variant A-T patients. We conclude that FCCM offers a robust ATM mutation detection method and can be used to screen for ATM mutations in cancer-prone populations.  (+info)

TY - JOUR. T1 - Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts. AU - Li, Yuling. AU - Carty, Michael P.. AU - Oakley, Gregory G.. AU - Seidman, Michael M.. AU - Medvedovic, Mario. AU - Dixon, Kathleen. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Ataxia telangiectasia (A-T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses. The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM may play a role similar to that of DNA-PKcs in DSB repair ...
TY - JOUR. T1 - Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. AU - Degan, Paolo. AU - dIschia, Marco. AU - Pallardó, Federico V.. AU - Zatterale, Adriana. AU - Brusco, Alfredo. AU - Calzone, Rita. AU - Cavalieri, Simona. AU - Kavakli, Kaan. AU - Lloret, Ana. AU - Manini, Paola. AU - Pisanti, Maria Antonietta. AU - Vuttariello, Emilia. AU - Pagano, Giovanni. PY - 2007/6. Y1 - 2007/6. N2 - Objective: To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT). Methods: A set of oxidative stress endpoints were measured in 9 AT homozygotes, 16 AT heterozygotes (parents) and 83 controls (grouped in age ranges as for patients and parents, respectively). The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione (GSSG and GSH); and (c) plasma levels of glyoxal (Glx) and methylglyoxal (MGlx). Results: AT patients displayed a significant decrease in ...
Albany, US) DelveInsight has launched a new report on Ataxia Telangiectasia Pipeline. Ataxia Telangiectasia (AT) Pipeline Insight, 2020 report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects across the Ataxia Telangiectasia (AT) market. A detailed picture of the Ataxia Telangiectasia (AT) pipeline landscape is provided, which includes the disease overview and Ataxia Telangiectasia (AT) treatment guidelines. The assessment part of the report embraces in-depth Ataxia Telangiectasia (AT) commercial assessment and clinical assessment of the Ataxia Telangiectasia (AT) pipeline products from the pre-clinical developmental phase to the marketed phase. In the report, a detailed description of the drug is proffered including mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Ataxia Telangiectasia (AT) collaborations, licensing, mergers and acquisition, ...
TY - JOUR. T1 - DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection. AU - Lücke-huhle, Christine. AU - Hinrichs, Susanne. AU - Speit, Günter. PY - 1987/12. Y1 - 1987/12. N2 - During selection for methotrexate resistance, SV40-transformed human skin fibroblasts from patients with ataxia telangiectasia (A-T) underwent amplification of the dihydrofolate reductase (DHFR) gene, experienced nearly complete loss of the integrated SV40 sequences and showed a 3.6-fold increase in Ki-ras gene copy number. Over a period of months methotrexate-resistant (MTXr) A-T subclones were obtained, which were able to grow in progressively increasing MTX concentrations up to 100 μM. The ED50 values determined as the effective dose of MTX causing 50% growth inhibition in comparison to control cells increased from 3×10-2 μM for MTXs AT5BI-VA cells to 250 μM MTX for the MTXr AX100 subclone. In contrast, human skin fibroblasts of healthy individuals did ...
We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity.. ...
TY - JOUR. T1 - ATM mutations in patients with ataxia telangiectasia screened by a hierarchical strategy. AU - Sasaki, Tomonari. AU - Tian, Huaize. AU - Kukita, Yoji. AU - Inazuka, Masakazu. AU - Tahira, Tomoko. AU - Imai, Takashi. AU - Yamauchi, Masatake. AU - Saito, Toshiyuki. AU - Hori, Tada Aki. AU - Hashimoto-Tamaoki, Tomoko. AU - Komatsu, Kenshi. AU - Nikaido, Osamu. AU - Hayashi, Kenshi. PY - 1998/1/1. Y1 - 1998/1/1. N2 - ATM has been identified as a gene that is responsible for ataxia telangiectasia (AT), a pleiotropic disorder of autosomal recessive inheritance. While many mutations of this gene in AT patients of various ethnicities have been reported, data on Japanese patients are scarce. In this report, we present the results of a thorough survey of ATM mutations in 14 unrelated AT patients, with an emphasis on Japanese subjects. We used a hierarchical strategy in which we extensively analyzed the entire coding region of the cDNA. In the first stage, point mutations were sought by ...
Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already ...
Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already ...
Cellular response to DNA damage is critical to maintain genomic stability. When a double-strand break (DSB) occurs, the cell activates its checkpoint machinery to halt cell cycle progression and allow proper DSB repair (1). Without such response and repair, the cell will eventually undergo apoptosis or pass on its altered DNA to daughter cells. Checkpoints are enabled through sensing DNA damage, transducing damage signals, and activating effectors. Mechanisms by which DNA damage signals are initiated have begun to be revealed (1, 2) . PI-3-like kinases, including ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), and DNA-PK are believed to play central roles (3). ATM is mutated (lost or inactivated) in the human genetic disorder ataxia-telangiectasia and could be the primary kinase responsible for DSB signaling transduction. Structural chromatin changes activate ATM, which then phosphorylates itself (4). Activated, autophosphorylated ATM in turn phosphorylates the checkpoint ...
Our experimental results establish that tissues from Atm-deficient mice are under oxidative stress and suffer oxidative damage. We and others have identified defects in molecular pathways that lead to abnormalities in the response of cells to ionizing radiation, meiosis, and T cell development where DNA double-strand breaks occur (1, 3-5, 20-23). In addition, several reports have implicated ATM as a serine protein kinase that phosphorylates p53 and chk2, leading to cell cycle arrest after ionizing radiation (24-27). Why would defects in these pathways result in oxidative stress, especially in the adult brain? The majority of cells in the central nervous system are postmitotic and there is no evidence of DNA recombination or significant DNA double-strand breaks in the central nervous system in the absence of ionizing radiation. We infer that ATM also functions to protect biomolecules other than DNA from oxidative damage. Studies from many investigators have established that lipids and proteins ...
History: Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities; ATM is usually the major kinase for DNA harm recognition. to IR. Finally, airport deoxynucleotidyl transferase-dUTP chip end labels assay. Traditional western colony and blotting formation assay were utilized XL147 to measure the effects of caffeine in radiation-related apoptosis. All of the data had been examined with a two-tailed Students < 0.05. Outcomes Caffeine suppresses L2AX foci of RT4 cells open to ionizing light < 0.001). 4-Gy IR by itself lead in 24.1 5.0 foci per nucleus compared with 7.9 2.0 foci in the IR and caffeine combinatory treatment (< 0.001). 2-Gy and 4-Gy IR both created a considerably higher strength of L2AX foci in IR by itself treated cells likened to IR plus caffeine treated cells (= 0.047 and = 0.003, respectively) [Figure ?[Body1a1air conditioning unit1c]. Physique 1 Suppressive effects of caffeine on the formation of H2AX foci and 53BP1 foci in ...
Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. The estimated risk of cancer of all types among heterozygotes as compared with noncarriers was 3.8 in men and 3.5 in women, and that for breast cancer in women was 5.1. Among the blood relatives, women with breast cancer were more likely to have been exposed to selected sources of ionizing radiation than controls without cancer (odds ratio = 5.8, P = 0.005). Male and female blood relatives also had 3-fold and 2.6-fold excess mortality from all causes, respectively, from the ages of 20 through 59 years. Conclusions: ...
TY - JOUR. T1 - Myoclonic axial jerks for diagnosing atypical evolution of ataxia telangiectasia. AU - Nakayama, Tojo. AU - Sato, Yuko. AU - Uematsu, Mitsugu. AU - Takagi, Masatoshi. AU - Hasegawa, Setsuko. AU - Kumada, Satoko. AU - Kikuchi, Atsuo. AU - Hino-Fukuyo, Naomi. AU - Sasahara, Yoji. AU - Haginoya, Kazuhiro. AU - Kure, Shigeo. PY - 2015/3/1. Y1 - 2015/3/1. N2 - Background: Ataxia telangiectasia (A-T) is a common inherited cause of early childhood-onset ataxia, distinguished by progressive cerebellum malfunction, capillary vessel extension, and immunodeficiency. The diagnosis of A-T is sometimes difficult to establish in patients with atypical clinical evolution. Case report: We experienced a pediatric 12-years-old female patient, who was finally diagnosed with classic A-T, demonstrating progressive dystonic-myoclonic axial jerks with ataxia as a predominant clinical feature. Oculocutaneous telangiectasias and immune status were unremarkable. Her myoclonic jerks were spontaneous or ...
The Ataxia-telangiectasia mutated (ATM) gene encodes a multifunctional kinase, which is linked to important cellular functions. Women heterozygous for ATM mutations have an estimated relative risk of developing breast cancer of 3.8. However, the pattern of ATM mutations and their role in breast cancer etiology has been controversial and remains unclear. In the present study, we investigated the frequency and spectrum of ATM mutations in a series of sporadic breast cancers and controls from the Brazilian population. Using PCR-Single Strand Conformation Polymorphism (SSCP) analysis and direct DNA sequencing, we screened a panel of 100 consecutive, unselected sporadic breast tumors and 100 matched controls for all 62 coding exons and flanking introns of the ATM gene. Several polymorphisms were detected in 12 of the 62 coding exons of the ATM gene. These polymorphisms were observed in both breast cancer patients and the control population. In addition, evidence of potential ATM mutations was observed in 7
Ataxia Telangiectasia & Immunoglobulin M Decreased Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Read stories about Ataxia Telangiectasia on Medium. Discover smart, unique perspectives on Ataxia Telangiectasia and the topics that matter most to you like care coordination, cscw2019, eltern, healthcare, and hoffnung.
Synonyms for Ataxia-telangiectasia in Free Thesaurus. Antonyms for Ataxia-telangiectasia. 3 synonyms for ataxia: ataxy, dyssynergia, motor ataxia. What are synonyms for Ataxia-telangiectasia?
Yosef Shiloh, a David and Inez Myers professor in cancer research at Tel Aviv Universitys Sackler Faculty of Medicine, was selected to receive the 2011 Israel Prize, Israels most distinguished national honor. The prize is awarded by the Israeli Ministry of Education to Israeli citizens who have demonstrated excellence in their chosen profession. Earlier this year Shiloh was the first Israeli to receive the 51st annual G.H.A. Clowes Award from the American Association for Cancer Research. He was honored for his studies on the cellular DNA damage response and the rare genomic instability syndrome ataxia-telangiectasia.. Shiloh has been investigating ataxia-telangiectasia and the defect in the DNA damage response that leads to this disease for more than 30 years. He revolutionized the field when his lab identified the ataxia-telangiectasia gene in 1995 and successfully cloned it, calling it ataxia-telangiectasia mutated. The identification of the ATM gene opened many new avenues of inquiry and ...
Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia A-T Patients Using a LC-MS-Based Label-Free Protein Quantification Technology. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
BackgroundAtaxia telangiectasia (A-T) is a common genetically inherited cause of early childhood-onset ataxia. The infrequency of this disease, vast phenotype variation, disorders with features similar to those of A-T, and lack of definite laboratory test, make diagnosis difficult. In addition, there is no rapid reliable laboratory method for identifying A-T heterozygotes, who susceptible to ionizing radiation (IR), atherosclerosis, diabetes, and cancers. We used SMC1pSer966 (pSMC1) in-cell colorimetric ELISA to diagnosis and screen in A-T families.Materials and Methods: With informed consent, 2cc peripheral blood was collected from the 15 A-T patients, their parents, and 24 healthy controls with no family history of malignancy, diabetes, and atherosclerosis. Extracted peripheral blood mononuclear cells (PBMCs) were cultured in poly-L-Lysine treated 96-well plate with density of 70,000 cells per well. SMC1 phosphorylation was evaluated with cell-based ELISA kit 1 hour after 5 Gy IR and the pSMC1data
In a critical process known as the DNA damage checkpoint, cells monitor their DNA for damage and halt cell division until the damage has been repaired. Kondo et al. (p. 867) now show that two yeast proteins that function in signaling that DNA damage has occurred actually bind close to the site of damage, but do so in distinct ways. They used a chromatin immunoprecipitation method to detect proteins that bound to double-stranded break in the DNA resulting from continuous expression of the HO endonuclease. One of the proteins bound, Mec1, belongs to a family of protein kinases that includes the ATM protein mutated in the human disease ataxia telangiectasia. Another protein bound at the site of damage was Ddc1, itself thought to be a DNA-binding protein that may recruit other proteins to a complex formed at the damage site. Recruitment of Ddc1, but not that of Mec1, required the action of another participant in the checkpoint pathway, called Rad24. The results help clarify how cells recognize ...
Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates a …
Ravi, Srimadhavi; Barui, Sugata and Kirubakaran, Sivapriya, Targeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancer, in the 68th Gordon Research Conference for Natural Products and Bioactive Compounds, Proctor Academy, Andover, NH, US, Jul. 28- Aug. 2, 2019 ...
Ataxia Telangiectasia (A-T) - Action for A-T funds high quality peer reviewed medical research to speed up the process of identifying a cure for A-T.
A fact sheet about ataxia telangiectasia (A-T), a rare, recessive genetic disorder of childhood that occurs in between one out of 40,000 and one out of 100,000 persons worldwide.
Falck et al. have made progress in defining the molecular mechanism underlying the S-phase checkpoint activated by ionizing radiation (IR). IR caused rapid, transient degradation of the phosphatase Cdc25A (which dephosphorylates and activates cyclin-dependent kinase 2) in mammalian cells by a mechanism dependent on the catalytic activity and the ability of the kinase Chk2 to interact with and phosphorylate Cdc25A. Furthermore, the degradation of Cdc25A in response to IR occurred in cells with normal and mutated versions of the tumor suppressor p53, confirming the independence of this S-phase checkpoint on the p53 pathway. However, in cells from patients with ataxia telangiectasia with mutations in the ATM gene, Cdc25A persisted after IR, and the cells exhibited radioresistant DNA synthesis. Thus, IR appears to activate a pathway from ATM to Chk2, which then phosphorylates Cdc25A leading to its destruction and a transient block in the progress of the S phase of the cell cycle. J. Falck, N. ...
Ataxia-telangiectasia (AT or A-T), also referred to as ataxia-telangiectasia syndrome or Louis-Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. A-T affects many parts of the body: It impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination. It weakens the immune system, causing a predisposition to infection. It prevents repair of broken DNA, increasing the risk of cancer. Symptoms most often first appear in early childhood (the toddler stage) when children begin to walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting, and may appear almost as if they are drunk. In late pre-school and early school age, they develop difficulty moving their eyes in a natural manner from one place to the next (oculomotor ...
Ataxia Telangiectasia is a progressive degenerative disease which affects various systems of the body. First signs of the disease usually appear during the second year of life.
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Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a proteins kinase Igf1 Everolimus that has a significant function in the activation of cellular replies to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. for breasts cancers remain unresolved. SOLUTIONS TO investigate the function of ATM in BC susceptibility we examined 76 uncommon sequence variations in the ATM gene within a case-control family members research of 2 570 situations of breasts cancers and 1 448 handles. The variations had been grouped into three types predicated on their most likely pathogenicity as dependant on in silico evaluation and examined by conditional logistic regression. Most likely pathogenic sequence variations had been genotyped in 129 family of 27 carrier probands (15 which transported c.7271T > G) and improved segregation analysis was utilized to estimation the BC penetrance connected with these uncommon ...
Initial presentation usually is neurologic as evidenced by problems with development of walking, oculomotor abnormalities, and progressive neurologic disability. Risk of recurrent aspiration of oral secretions. In addition to telangiectasia, vitiligo, café-au-lait spots, and premature graying may be present. Absence of secondary sexual characteristics in females. Elevated liver enzymes associated with fatty infiltration of the liver. Ataxia telangiectasia patients are at increased risk for developing malignancies, particularly lymphoma and leukemia in children and gastric carcinoma in adults. Chronic respiratory infections and bronchiectasis, unresponsive to antibiotics, are frequently the ultimate cause of death. Unusual to survive beyond the third decade. ...
The effect of ataxia-telangiectasia mutated kinase-dependent hyperphosphorylation of checkpoint kinase-2 on oligodeoxynucleotide 7909 containing CpG motifs-enhanced sensitivity to X-rays in human lung adenocarcinoma A549 cells Xiaoqun Liu,1,* Xiangdong Liu,2,* Tiankui Qiao,1 Wei Chen,1 Sujuan Yuan1 1Department of Oncology, 2Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The aim of the study reported here was to further investigate the potential effect of ataxia-telangiectasia mutated (ATM) kinase-dependent hyperphosphorylation of checkpoint kinase-2 (Chk2) on radiosensitivity enhanced by oligodeoxynucleotide 7909 containing CpG motifs (CpG ODN7909) in human lung adenocarcinoma A549 cells. Methods: In vitro A549 cells were randomly separated into control, CpG, X-ray, CpG+X-ray, ATM kinase-small interfering RNA (siRNA)+CpG+X-ray (ATM-siRNA), and Chk2-siRNA+CpG+X-ray
A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the
Ataxia-Telangiectasia (A-T) is an inherited disease that affects several body systems, including the immune system. People with A-T have an unsteady, wobbly gait (ataxia) that gets worse as they get older; dilated, corkscrew-shaped blood vessels (telangiectasia) on the whites of the eyes and on sun-exposed areas of skin; immunodeficiency involving both humoral (B-lymphocytes) and cellular (T-lymphocytes) immunity; and a high rate of cancer.
Methuselah Co., set up in Yamagata in June 2016, has developed technology to produce autologous fibroblast cells, a cell type which which can be blended with other functional cells to develop regenerative medicine of various types.. BioImpact news release, July 7, 2016. ...
Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative...
The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. The authors previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; they now report that increased trimethylation of histone H3 on Lys27 (H3K27me3) mediated by polycomb repressive complex 2 is also important in the A-T phenotype. [Nat Neurosci ...
An inherited (autosomal recessive) neurological disorder. Ataxia is usually noted early in life, and a key feature is the presence of dilated blood vessels visible in the sclerae of the eyes and on the cheeks and ears. Other symptoms may include slow slurred speech, abnormal eye movements, skin lesions, and immune deficiency. Affected individuals may develop malignant disease. A raised level of alpha-fetoprotein is found in the blood. ...
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Ceralasertib is a potent and selective ATP competitive inhibitor of ataxia telangiectasia and Rad3 related (ATR) in clinical development as monotherapy and in combination with olaparib (Lynparza) and durvalumab (Imfinzi) in patients with advanced solid tumors. Paired pre- and on-treatment tumour samples from seven patients during ceralasertib monotherapy in Phase 1 studies (NCT02223923, NCT02264678), all ATM expressing, showed increases in pRAD50 on treatment. This study aimed to robustly understand the relationship between ceralasertib pharmacokinetics, pRAD50 (pSer635) induction by immunohistochemistry and anti-tumor efficacy, in mouse xenografted models; to enable interpretation of paired clinical tumour samples. First, in vivo data were generated in a range of xenografted models (HBCx9 [TNBC, Xentech], HCC1806 [BC], OCI-Ly19 [DLBCL] and OE21 [HNSCC]) and NSCLC and HNSCC PDX models at Champions). Mouse ceralasertib doses (6.25 - 25mg/kg BID and 50mg/kg QD) reflected the observed free drug ...
TY - JOUR. T1 - Apurinic DNA endonuclease activities in repair-deficient human cell lines. AU - Moses, Robb. AU - Beaudet, Arthur L.. PY - 1978/2. Y1 - 1978/2. N2 - Several autosomal recessive diseases are associated with apparent DNA repair defects in cell culture. It seemed likely that a defect in excision repair reported for ataxia telangiectasia cells might reflect a lack of apurinic endonuclease activity. We report here normal levels of apurinic endonuclease activity in extracts of cell lines derived from patients with ataxia telangiectasia, xeroderma pigmentosum (complementation group D), Cockayne dwarfism, Fanconi anemia and Bloom syndrome.. AB - Several autosomal recessive diseases are associated with apparent DNA repair defects in cell culture. It seemed likely that a defect in excision repair reported for ataxia telangiectasia cells might reflect a lack of apurinic endonuclease activity. We report here normal levels of apurinic endonuclease activity in extracts of cell lines derived ...
TY - JOUR. T1 - Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) protein to regulate intra-S-phase checkpoint. AU - Lee, Alan Yueh Luen. AU - Chiba, Takuya. AU - Truong, Lan N.. AU - Cheng, An Ning. AU - Do, Johnny. AU - Cho, Michael Jeffrey. AU - Chen, Longchuan. AU - Wu, Xiaohua. N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2012/1/20. Y1 - 2012/1/20. N2 - Dbf4/Cdc7 (Dbf4-dependent kinase (DDK)) is activated at the onset of S-phase, and its kinase activity is required for DNA replication initiation from each origin. We showed that DDK is an important target for the S-phase checkpoint in mammalian cells to suppress replication initiation and to protect replication forks. We demonstrated that ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) proteins directly phosphorylate Dbf4 in response to ionizing radiation and replication stress. We identified novel ATM/ATR ...
Salt Lake City - Recursion Pharmaceuticals, an emerging biotech company today announced receipt of a research award from the A-T Childrens Project, which seeks to support research for the disease ataxia-telangiectasia.. Ataxia-telangiectasia (A-T) is a rare genetic disease that attacks children, causing progressive loss of muscle control, immune system problems, and a high rate of cancer. The award will be used to support Recursions efforts to build a many-dimensional cellular model of the disease to be used in future drug screening efforts.. Chris Gibson, Ph.D., CEO of Recursion Pharmaceuticals remarked: We are grateful to the A-T Childrens Project for this award which will enable us to rapidly deploy our innovative drug discovery technology towards Ataxia-telangiectasia. As a young company, the support and trust of foundations like the A-T-Childrens Project is critical to our ability to apply our technology across as many diseases as possible.. Recursions technology, which combines ...
TY - JOUR. T1 - Hodgkin lymphoma in a young child contributing to a diagnosis of ataxia telangiectasia. T2 - Review of the literature. AU - Hummel, Jennifer M.. AU - Thorland, Erik C. AU - Lim, Megan S.. PY - 2010. Y1 - 2010. N2 - Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, chromosomal instability, and radiation sensitivity (Peterson et al. Lancet 283:1189-1193, 1964; Boder and Sedgwick Pediatrics 21:526-554, 1958; Taylor et al. Nature 258:427-429, 1975). Compared to the general population, patients with primary immunodeficiencies such as A-T have an increased rate of malignancy and an earlier age at presentation (Loeb et al. J Pediatr Hematol/Oncol 22:464-467, 2000; Taylor et al. Blood 87:423-438, 1996). We report the clinical, histopathologic, and molecular features of a 6-year-old child who presented with EBV-positive Hodgkin lymphoma (HL), which led to the diagnosis of ataxia ...
View more ,Ataxia Telangiectasia is a progressive neurodegenerative disorder caused by mutations in the ataxia telangiectasia mutated (atm) gene. Nuclear ATM has a well established role in response to DNA damage, however ATM has also been localized outside the nucleus where it has been demonstrated to participate in the insulin signalling pathway by phosphorylating eIF-4E binding protein(4EBP1). 4EBP1 is a target of Mammalian target of Rapamycin (mTOR) and its phosphorylation releases it from eIF-4E enabling translation of mRNA and protein synthesis. The Tuberous Sclerosis Complex (TSC) proteins, hamartin (TSC1) and tuberin (TSC2) act as a heterodimer to regulate mTOR activity. mTOR exists as two complexes, mTORC1 (rapamycin sensitive) and mTORC2 (insensitive to short term rapamycin). These complexes control many cellular functions including protein synthesis, autophagy, lipid metabolism, mitochondrial biogenesis and cytoskeletal organisation. Mutations in either of the TSC1 or TSC2 genes lead ...
The kinase ATM is classically known for its role in coordinating the response to DNA damage. DNA damage is caused by various intracellular and extracellular stimuli, including oxidative stress and free radicals. Lee et al. found critical amino acid residues that enable ATM to coordinate a response to DNA damage that is independent of its response to oxidative stress. Activation of ATM by either pathway promoted mitochondrial function and autophagy, thus mediating cell survival through metabolic changes. ATM activation via oxidative stress additionally promoted the clearance of toxic protein aggregates. These findings expand the roles of ATM and suggest that the loss of ATM function, such as in the neurodegenerative disease ataxia telangiectasia (A-T), causes broader cellular stress than that limited to a defective DNA damage response. ...
Minnie Geller Professor. research • lab members • publications. Google Scholar Profile. Representative Publications:. Strand, M., Prolla, T. A., Liskay, R. M. and Petes, T. D. (1993). Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274-276.. Fan, Q.-Q., Xu, F. and Petes, T. D. (1995). Meiosis-specific double-strand DNA breaks at the HIS4 recombination hotspot in the yeast Saccharomyces cerevisiae. Mol. Cell. Biol. 15:1679-1688.. Greenwell, P. W., Kronmal, S. L., Porter, S. E., Gassenhuber, J., Obermaier, B., and Petes, T. D. (1995).TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82:823-829.. Kirkpatrick, D. and Petes, T. D. (1997). Repair of DNA loops involves DNA mismatch and nucleotide excision repair proteins. Nature 387:929-931.. Moore, H., Greenwell, P. W., Liu, C.-P., Arnheim, N., and Petes, T. D. (1999). Triplet repeats form secondary ...
Mutations in the ATM gene have previously been identified in CLL tumours. In this project, I have demonstrated that their detection would have prognostic value. With a prevalence of 12%, ATM mutations represent the commonest single gene defect to be detected in CLL tumours and they identified a subgroup of CLL patients that had a significant reduction in both treatment free and overall survival. Furthermore, ATM mutations provided prognostic information that was independent of age, clinical stage, the mutation status of the IGVH genes and TP53 mutations. The temporal acquisition of the ATM mutations and their relationship with loss of an ATM allele via a chromosomal 11q deletion provides clues into their mechanism of action. There was only a partial correlation between CLL tumours with mutations in the ATM gene and those with a chromosome 11q deletion. In certain cases, the ATM mutations represented germ-line changes and in others were acquired very early in the disease course raising the ...
Definition of ataxia telangiectasia syndrome. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
Ataxia-telangiectasia (A-T) is a rare, autosomal recessive human disorder characterized by cerebellar ataxia, immunodeficiency, cancer predisposition, recurrent...
TOPICS: ATM gene, double-stranded DNA breaks, nonhomologous end joining repair mechanism, cell cycle, mutations, alpha-fetoprotein (AFP), autosomal recessive, cerebellar atrophy, ataxia, spider angiomas (telangiectasias), IgG, radiation, IgA, lymphopenia, lymphoma, leukemia, T cell disorder, B cell disorder, IgE ...
Different excellence centers in Italy and in the world are involved in research projects aimed to define the role of ATM protein in the AT physiopathology the ATM protein. To know the mechanisms that lead to neurodegeneration as a result of the lack of ATM and basilar protein to understand the symptoms of the patients with AT and to propose new therapeutic strategies. ANAT finances for years the following research projects:. In the last years it was proposed that ATM protein is involved in defense mechanisms to oxidative stress and in metabolism.. Projects title: The role of ATM in the control of cellular metabolism Scientific responsible: Doc. Vincenzo Costanzo. Host institute: IFOM, FIRC Institute of Molecular Oncology (Milan). The molecular basis of corticosteroids efficiency in the improvement of neurological symptoms at patients with AT are still research objects.. Project title: Corticosteroids for patients with Ataxia Telangiectasia (AT): the dexamethasone effect on AT cells activity ...
DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a multi-systemic, recessively inherited disorder that affects between 1 in 40,000 to 1 in 100,000 individuals worldwide. It is characterized primarily by early onset cerebellar ataxia andtelangiectasia, from which the disease name is derived. In addition, patients also exhibit a number of other clinical symptoms including increased susceptibility to cancer (lymphomas, leukemia, brain tumors), immunodeficiency, insulin-resistant diabetes, chromosomal instability, sensitivity to ionizing radiation, susceptibility to bronchopulmonary disease, and the absence, or almost complete absence, of a thymus. Current treatments for A-T are directed toward the management of symptoms. Physical and speechtherapy can improve the lives of patients, and -globulin injections can be given to support the immune system. However, no treatment is directed at the underlying defect. Consequently, A-T remains a fatal disease. The development of improved ...
We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei. ...
R. John Davenport http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/9/nw35 Key Words: genomic instability ATR ATM Ataxia telangiectasia DNA repair double-strand breaks RAD26 DDC2. Abstract: In eukaryotic cells, protein sentries ensure that the genome is complete before cell division proceeds. When DNA is damaged or its replication machinery conks out, the genome guardians attach phosphate groups to other proteins; this chemical addition triggers these proteins to bring the cell cycle to a halt and activate DNA repair machinery. A breakdown in this system can impair health: People with a defective copy of the gene for one of those proteins--called ATM--suffer from a disorder known as ataxia telangiectasia (see Transgenic Mouse Entries: tg1, tg2, and tg3). Symptoms of the disorder include neuronal degeneration, weakened immunity, and increased risk of cancer. Although scientists know a fair amount about ATM, key information is missing about the activities of a related ...
ATM has been shown to have important roles in the transcriptional regulation of gene expression by phosphorylation of transcription factors, such as p53, nuclear factor κB, E2F, cyclic AMP-responsive element binding protein, and BRCA1, and in maintenance of the normal functions of IGF-IR and telomeres (3, 13, 14, 32). ATM-dependent gene expression has been systematically studied by comparing cell lines from normal individuals and AT patients, isogenic cell lines with restoration of ATM in AT cells or small interfering RNA knockdown of ATM in wild-type cells, and ATM+/+/ATM−/− mice (3, 13, 21-23). More than 300 genes have been reported to display ATM-dependent expression although few genes were commonly identified in two or more experiments. The microarray results presented here identified 160 genes or expressed sequence tags (∼1% of the total on the array) that were differentially expressed in normal and AT fibroblast lines under basal growth conditions, of which about half were ...
In previous research, we have demonstrated that tobacco smoke condensate (CSC), a surrogate for tobacco smoke, is with the capacity of changing the spontaneously immortalized human being breasts epithelial cell line, MCF10A. and is recognized as a marker for improved tumor quality 105628-72-6 and nodal metastasis (Olopade gene appearance in MCF10A cellular material. Our results recommend, for the very first time to our understanding, that C/EBP binds the promoter and induces its activity in MCF10A cellular material in response CSC treatment. Outcomes CSC treatment induces bcl-xl mRNA and proteins amounts in MCF10A cellular material To look for the aftereffect of CSC treatment on gene amounts, we treated MCF10A cellular material with increasing levels of CSC for 24 h and mRNA amounts had been assessed by RT-PCR (Fig. 1A). In these cellular material after normalization with mRNA, the mRNA appearance slightly reduces at lower concentrations (2.5 g/mL) and improves at higher concentrations of CSC ...
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Ataxia telangiectasia (A-T) is a rare, recessive, neurodegenerative disease, with symptoms that normally appear in early childhood. Initial indications are usually ataxia (a lack of muscle control leading to loss of balance and coordination) and telangiectasia (tiny red veins, which are most noticeable on the whites of the eyes). The most serious clinical problem is loss of Purkinje cells, leading to degeneration of the cerebellum (the bodys motor control centre). About 70% of sufferers also have thymic hypoplasia and a compromised immune system. Patients are also highly sensitive to X-irradiation and are susceptible to malignant tumors. Currently, there is no cure, nor any treatment that halts the progression of the disease.. A-T is caused by mutation of the ATM gene, which encodes a ubiquitous 370-kD serine-threonine kinase that is essential for normal repair of double-stranded DNA breaks; loss of ATM function results in DNA instability. However, there are atypical cases of A-T in which ATM ...
Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATMs potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% ...
About 1.4% of the general population are heterozygous carriers of the gene for ataxiatelangiectasia (A-T), an autosomal recessive progressive neurologic syndrome in which cancer incidence of homozygotes is approximately 100-fold greater than the general populations rates. The hypothesis that A-T he …
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Ataxia Telangiectasia Mutated protein kinase (ATM) has lately come to the fore as a regulatory protein fulfilling many roles within…. Continue Reading →. ...
Abstract Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the […]. ...
Possibly Dystonia Only Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
I was diagnosed with A-T when I was 3 years old. Since 1999, my family and many friends have raised money for the A-T Childrens Project by participating in numerous walks, golf tournaments, and marathons. All of this was done on my behalf. My Pool Challenge is my way of giving back to all our supporters as well as making a difference for A-T people everywhere.. This year I am also walking to honor my dear friend, Kate, who passed early this summer. We met over 12 years ago at an A-T marathon weekend and were fast friends from then on. I know Kate will be cheering for me on July 24. And I will certainly be thinking of her while I walk!. My goal is to raise enough money so the A-T Childrens Project can fund more research to find a cure or treatment for A-T.. ...
Natalie Cole believed blood relatives arent the only ones worthy of being remembered in a will ... she is taking care of 2 friends who took good care of…
Hello, I just found out that I am K01a-T195C! Can anyone explain this classification for me?Am I just K1a or should there be more? What does the T195C! mutation mean?
Ataxia telangiectasia mutated kinase (ATM kinase)[edit]. ATM kinase, a member of the PI3-like family of serine/threonine ...
Ataxia-telangiectasia). peripheral: Purine nucleoside phosphorylase deficiency *Hyper IgM syndrome (1). Severe combined. (B+T) ...
Ataxia-telangiectasia). peripheral: Purine nucleoside phosphorylase deficiency *Hyper IgM syndrome (1). Severe combined. (B+T) ...
Patients with Ataxia telangiectasia delays have hypersensitivity to radiation due to the delay of accumulation of p53. In this ... "Ataxia Telangiectasia". National Cancer Institute. Retrieved 2016-04-11. Soriani RR, Satomi LC, Pinto Td (2005-07-01). "Effects ...
"ataxia-telangiectasia". Genetics Home Reference. Retrieved 2017-05-15. "What Is Fanconi Anemia?". NHLBI, NIH. Retrieved 2017-05 ... Mutations in the ATM gene cause ataxia-telangiectasia. The ATM gene provides instructions for making a protein that helps ...
... the ataxia telangiectasia service; services for patients with pulmonary fibrosis, vasculitis, and rare diseases including ...
Taylor AM, Byrd PJ (October 2005). "Molecular pathology of ataxia telangiectasia". Journal of Clinical Pathology. 58 (10): 1009 ... the liver Nonseminomatous germ cell tumors Yolk sac tumor Other conditions associated with elevated AFP Ataxia telangiectasia: ...
1996). "Accelerated telomere shortening in ataxia telangiectasia". Nat. Genet. 13: 350-353. doi:10.1038/ng0796-350. Hastie ND, ...
"N-Acetyl-L-Leucine for Ataxia-Telangiectasia". clinicaltrials.gov. Retrieved 2019-08-01. "IntraBio". Retrieved 2019-08-01. ... parallel clinical trials with N-Acetyl-L-Leucine for the treatment of Niemann-Pick disease type C and Ataxia-Telangiectasia. ...
"Entrez Gene: NPAT nuclear protein, ataxia-telangiectasia locus". Zheng L, Roeder RG, Luo Y (Jul 2003). "S phase activation of ... half of the gene for ataxia telangiectasia". Human Molecular Genetics. 5 (1): 145-9. doi:10.1093/hmg/5.1.145. PMID 8789452. ...
"The Ataxia-Telangiectasia Society Annual Report and Accounts" (PDF). 2014. "Information for ICRR2015". Journal of Radiation ... In 2014, Jeggo was the chair of the Scientific Advisory Board for the Ataxia-Telangiectasia Society. Jeggo was an invited ... She found that a mutation in ataxia telangiectasia mutated kinase (ATM) causes damage to DNA and chromatin structure. Jeggo's ... In her most recent publication, Jeggo worked with other researchers on the Ataxia telangiectasia and Rad3 related protein (ATR ...
... ataxia telangiectasia. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). EZH2's catalytic activity ... "EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia". Nat. Neurosci. 16 (12): 1745-53. doi: ...
However, research has linked SH3D21 expression changes to male infertility and Ataxia Telangiectasia. Further studies have ... "Newborn screening for SCID identifies patients with ataxia telangiectasia". Journal of Clinical Immunology. 33 (3): 540-9. doi: ...
Mutations of Mre11 can precipitate ataxia-telangiectasia-like disorder. V(D)J recombination involves opening stem-loops ...
Ataxia-telangiectasia. Secondary immune deficiencies. *AIDS. AllergiesEdit. Main article: allergy. An allergy is an abnormal ...
Ataxia-telangiectasia is due to mutation in the Atm gene. Wild-type Atm encodes a protein kinase employed in chromatin ... "Nuclear accumulation of HDAC4 in ATM deficiency promotes neurodegeneration in ataxia telangiectasia". Nat. Med. 18 (5): 783-90 ... and altered neuronal gene expression that likely contributes to the neurodegeneration characteristic of ataxia-telangiectasia. ...
... has been shown to interact with: FANCI Ataxia telangiectasia mutated, BARD1, BRCA1. BRCA2, FANCE, HTATIP, and MEN1. ... Castillo P, Bogliolo M, Surralles J (May 2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in ... May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell. 109 (4): 459-72. doi:10.1016 ... May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell. 109 (4): 459-72. doi:10.1016 ...
1989). "Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia". Ann. Neurol. 24 (4): 497-502. doi:10.1002/ana ... GeneReviews/NCBI/NIH/UW entry on Ataxia with Oculomotor Apraxia Type 1 OMIM entries on Ataxia with Oculomotor Apraxia Type 1 ... 2005). "The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break ... Ataxia oculomotor apraxia-1 is a neurological disorder caused by mutations in the APTX gene that encodes aprataxin. The ...
He had been suffering for many years of Ataxia telangiectasia. She also came out some time later as a lesbian. She has made a ...
Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, Elledge SJ (2000). "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo ...
August 2006). "ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles". Nat. Genet. 38 (8): ...
Genetic diseases, like Klinefelter syndrome, Chédiak-Higashi syndrome, ataxia-telangiectasia syndrome. Autoimmune diseases, ...
... has been shown to interact with Mdm2 and Ataxia telangiectasia mutated. Abnormalities in this gene are one of the causes ...
"Splicing Defects in the Ataxia-Telangiectasia Gene, ATM: Underlying Mutations and Consequences". The American Journal of Human ...
2000). "Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products". Nature. 405 (6785): 473-7 ...
... including Ataxia telangiectasia, B-cell defects, Epidermolysis bullosa, and X-linked agammaglobulinemia. Xeroderma pigmentosum ... "Splicing Defects in the Ataxia-Telangiectasia Gene, ATM: Underlying Mutations and Consequences". The American Journal of Human ...
Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (2000). "Functional link of BRCA1 and ataxia telangiectasia ... "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response". Nature. 406 (6792): 210-5. doi:10.1038 ...
"A randomized trial of oral betamethasone to reduce ataxia symptoms in ataxia telangiectasia". Movement Disorders. 27 (10): 1312 ... symptoms associated with ataxia telangiectasia (A-T) by 28-31%. Betamethasone is also used to stimulate fetal lung maturation ... In a randomized controlled trial betamethasone was shown to reduce some of the ataxia (poor coordination) ...
Tauchi H, Green C, Knapp M, Laderoute K, Kapp L (2000). "Altered splicing of the ATDC message in ataxia telangiectasia group D ... Hosoi Y, Kapp LN (1994). "Expression of a candidate ataxia-telangiectasia group D gene in cultured fibroblast cell lines and ... Laderoute KR, Knapp AM, Green CJ, Sutherland RM, Kapp LN (1996). "Expression of the ATDC (ataxia telangiectasia group D- ... Leonhardt EA, Kapp LN, Young BR, Murnane JP (1994). "Nucleotide sequence analysis of a candidate gene for ataxia-telangiectasia ...
Reduced activity of this enzyme may also play a role in ataxia-telangiectasia. Alternative splicing of this gene results in two ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Ataxia telangiectasia mutated,[58]. *BARD1,[59]. *BRCA1,[59][60][61][62]. *BRCA2,[52][59][60][63][64][65][66][67][68][69][70][ ...
Ataxia telangiectasia. بیماری‌های نورون حرکتی. *نورون حرکتی فوقانی فقط: *Primary lateral sclerosis ...
Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription, is a ...
Inherited immune deficiency - severe combined immunodeficiency, common variable immune deficiency, ataxia-telangiectasia, ...
Wiskott-Aldrich syndrome DNA repair defects not causing isolated SCID: ataxia-telangiectasia, ataxia-like syndrome, Nijmegen ...
Poor balance or coordination due to cerebral ataxia.[5]. *Eye defects such as coloboma or ptosis.[10] ... TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia). *TGFBR1/TGFBR2 (Loeys-Dietz syndrome) ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Ataxia telangiectasia mutated. *mTOR. *EIF-2 kinases *PKR. *HRI. *EIF2AK3. *EIF2AK4. *Wee1 *WEE1 ...
ATM: ataxia telangiectasia mutated (includes complementation groups A, C and D). *CD81 ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
This patient presented with progressive dementia, ataxia and incontinence. A clinical diagnosis of normal pressure ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Neuropathy, ataxia, and retinitis pigmentosa. References[edit]. *^ a b c d e f g h i j k l m n o p q "Leigh syndrome". Genetics ... Hypotonia (low muscle tone and strength), dystonia (involuntary, sustained muscle contraction), and ataxia (lack of control ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
... ataxia-telangiectasia (sensory and cerebellar, with the latter predominating), and abetalipoproteinaemia. An example of X- ... See also: Cerebellar ataxia. The term cerebellar ataxia is used to indicate ataxia due to dysfunction of the cerebellum.[2] The ... Hereditary disorders causing ataxia include autosomal dominant ones such as spinocerebellar ataxia, episodic ataxia, and ... of ataxias of unknown origin and 15% of all ataxias.[31] Less than 10% of people with gluten ataxia present any ...
Identical twin with ALL, Down syndrome, Fanconi anemia, ataxia telangiectasia, Klinefelter syndrome, high birth weight, ... ataxia-telangiectasia, paroxysmal nocturnal hemoglobinuria, and Li-Fraumeni syndrome.[13] Fewer than 5% of cases are associated ...
Ataxia telangiectasia. *Incontinentia pigmenti. *Peutz-Jeghers syndrome. *Encephalocraniocutaneous lipomatosis. *v. *t. *e ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
It is then distinguished by the development of myoclonus as well as seizures and ataxia in some cases.[20] ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Gall gwrthimiwnedd nad yw'n fwriadol ddigwydd mewn, er enghraifft, ataxia-telangiectasia, sawl math o ganser, a heintiau cronig ...
Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Ataxia telangiectasia. *De Barsy syndrome. *PIBI(D)S syndrome. *BIDS syndrome. *Marfanoid-progeroid-lipodystrophy syndrome ... telangiectasia; and malignancies.[3][9] In fact, the prevalence of rare cancers, such as meningiomas, are increased in ...
Mental retardation arachnodactyly hypotonia telangiectasia. *Mental retardation athetosis microphthalmia. *Mental retardation ... Luteinizing hormone releasing hormone, deficiency of with ataxia. *Lutz Richner Landolt syndrome ...
ataxia (Poor coordination / unsteady walking). A variant with combined features of MSA and Lewy body dementia may also exist.[ ... characterized by progressive ataxia (an inability to coordinate voluntary muscular movements) of the gait and arms and ... MSA with cerebellar features (MSA-C). MSA-C is defined as MSA where cerebellar ataxia predominates. It is sometimes termed ... Other common signs at onset include problems with balance (cerebellar ataxia) found in 22% at first presentation, followed by ...
Unlike ataxia, which affects the quality of voluntary movements, or Parkinsonism, which is a hindrance of voluntary movements, ... the spinocerebellar ataxias type 1, 3 and 17, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron ... accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia, mitochondrial disease and Rett ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ...
Ataxia telangiectasia is a rare genetic condition. Children with the condition have uncoordinated movements that get worse over ... What Causes Ataxia-Telangiectasia?. Ataxia-telangiectasia happens when a change (mutation) in the gene that makes a protein ... How Is Ataxia-Telangiectasia Treated?. Children with ataxia-telangiectasia are cared for by a health care team. They include ... How Is Ataxia-Telangiectasia Diagnosed?. Doctors might suspect ataxia-telangiectasia when a child has an unsteady walk, unusual ...
Ataxia Telangiectasia (AT) is an inherited disease that affects several body systems, including the nervous system and immune ... About Ataxia-Telangiectasia (Ataxia-Telangiectasia Childrens Project) * Ataxia - telangiectasia (Medical Encyclopedia) Also in ... Ataxia Telangiectasia (National Institute of Neurological Disorders and Stroke) * Ataxia-Telangiectasia (For Parents) (Nemours ... Ataxia-telangiectasia (A-T) is a rare, inherited disease. It affects the nervous system, immune system, and other body systems ...
Ataxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. ... medlineplus.gov/genetics/condition/ataxia-telangiectasia/ Ataxia-telangiectasia. ... Ataxia-telangiectasia is inherited in an autosomal recessive pattern. , which means both copies of the ATM gene in each cell ... ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6. Review. Citation on PubMed or Free article on PubMed Central ...
A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and ...
Ocular manifestations of ataxia-telangiectasia.. Farr AK1, Shalev B, Crawford TO, Lederman HM, Winkelstein JA, Repka MX. ... To report the manifestations of ataxia-telangiectasia (A-T) on the ocular sensory and motor systems. ...
... cutaneous telangiectasia and cancer syndrome, familial); FRP1 (FRAP-related protein-1); MEC1 (mitosis entry checkpoint 1); ... Ataxia Telangiectasia Mutate Replication Stress Origin Firing Stall Replication Fork Heat Repeat These keywords were added by ... Ataxia Telangiectasia and Rad3-related (ATR) or FRAP-related protein-1 (FRP1) is a 2644 amino acid protein kinase, located on ... Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers. Genes ...
... cerebellar ataxia, variable immunodeficiency with susceptibility to sinopulmonary infections, impaired organ maturation, x-ray ... Ataxia-telangiectasia (A-T) is an autosomal recessive, complex, multisystem disorder characterized by progressive neurologic ... hypersensitivity, ocular and cutaneous telangiectasia (see image below), and a p... ... The ataxia-telangiectasia gene has been localized to band 11q22-23. The gene, called ATM (ataxia-telangiectasia mutated), is a ...
Definition of ataxia telangiectasia syndrome. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms ...
Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic problems that lead to difficulty ... Children with A-T may begin staggering and appear unsteady (called ataxia) shortly after learning to walk. Most ... What is Ataxia-Telangiectasia?. Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic ... The gene associated with A-T is ATM, meaning ataxia telangiectasia mutated. Mutations (changes) in the ATM gene cause A-T. ...
Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Ari Elson, Yaoqi Wang, Cathie J. Daugherty, Cynthia C. ... Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Ari Elson, Yaoqi Wang, Cathie J. Daugherty, Cynthia C. ... Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Ari Elson, Yaoqi Wang, Cathie J. Daugherty, Cynthia C. ... Pleiotropic defects in ataxia-telangiectasia protein-deficient mice Message Subject (Your Name) has sent you a message from ...
... is an autosomal recessive genetic disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, and ... in the literature was a 9-year-old child with progressive cerebellar ataxia and bilateral oculocutaneous telangiectasia re... ... encoded search term (Ataxia-Telangiectasia in Ophthalmology) and Ataxia-Telangiectasia in Ophthalmology What to Read Next on ... Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent ...
There are many forms of ataxia. Some ataxias are hereditary, some have other causes and sometimes ataxia can be a symptom of ... for treatment of ataxia telangiectasia and other inherited forms of ataxia are underway. For additional information, physicians ... Ataxia telangiectasia usually begins during infancy (between one and three years of age) and often affects more than one child ... Ataxia telangiectasia is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received ...
Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal ... Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. ...
The simultaneous absence of telangiectasias and of other nonneurological manifestations made ataxia-telangiectasia an unlikely ... Although the neurological signs were indistinguishable from those of ataxia-telangiectasia, the onset tended to be later and ... We report 14 patients with a slowly progressive syndrome featuring ataxia, choreoathetosis, and ocular motor apraxia in both ...
It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, ... The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ... The genetic defect in ataxia-telangiectasia Annu Rev Immunol. 1997;15:177-202. doi: 10.1146/annurev.immunol.15.1.177. ... The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ...
AT stands for Ataxia-Telangiectasia. AT is defined as Ataxia-Telangiectasia very frequently. ... DIAGNOSIS Ataxia-telangiectasia DISCUSSION Ataxia-telangiectasia (AT), also known as Louis-Bar syndrome, is a hereditary ... Eighth International Workshop on Ataxia-Telangiectasia (ATW8).. Ataxia telangiectasia and secondary diseases/Ataksi ... Comparison of ataxia-telangiectasia mutated protein expression in .... These conditions include molluscum, ataxia- ...
Make research projects and school reports about Ataxia-telangiectasia easy with credible articles from our FREE, online ... and pictures about Ataxia-telangiectasia at Encyclopedia.com. ... Ataxia-telangiectasia. Definition. Ataxia-telangiectasia (A-T) ... Ataxia-Telangiectasia. Definition. Ataxia-telangiectasia (A-T), also called Louis-Bar syndrome, is a rare, genetic neurological ... progressive ataxia and telangiectasia. However, this may be difficult as ataxia symptoms do appear prior to telangiectasia ...
Mutations at the ataxia-telangiectasia locus cause a distinctive autosomal recessive syndrome in homozygotes and predispose ... Carriers of mutations at the ataxia-telangiectasia locus, who make up 1.4% to 2% of the general population, have a higher ... 405 grandparents of patients with ataxia-telangiectasia.. MEASUREMENTS: Ages at death and risk for death (from all causes, ... Compared with noncarriers, carriers of a mutated ataxia-telangiectasia allele had a significantly increased risk for death at ...
A prevalence study of ataxia telangiectasia was conducted in the West Midlands, with a population of over 5 million. The ... Boder E (1985) Ataxia telangiectasia: an overview. In: Gatti RA, Swift M (eds) Ataxia telangiectasia. (Kroc foundation series, ... Swift M (1985) Genetics and epidemiology of ataxia telangiectasia.In: Gatti RA, Swift M (eds) Ataxia telangiectasia. (Kroc ... Taylor AMR (1982) Cytogenetics of ataxia telangiectasia. In: Bridges BA, Harnden DG (eds) Ataxia telangiectasia. Wiley, ...
Ataxia telangiectasia is a rare childhood disease that affects the nervous system and other body systems. ... What is ataxia telangiectasia?. Ataxia telangiectasia (A-T) is a rare, inherited disease that affects several organs and ...
... This article is missing citations or needs footnotes.Using inline citations helps guard against copyright ... Huntingtons disease - Spinocerebellar ataxia (Friedreichs ataxia, Ataxia telangiectasia, Hereditary spastic paraplegia). ... "Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent ... Ataxia-telangiectasia (AT) (Boder-Sedgwick syndrome[1] or Louis-Bar syndrome) is a primary immunodeficiency disorder that ...
People with A-T have an unsteady, wobbly gait (ataxia) that gets worse as they get older; dilated, corkscrew-shaped blood ... vessels (telangiectasia) on the whites of the eyes and on sun-exposed areas of skin; immunodeficiency involving both humoral (B ... Ataxia-Telangiectasia (A-T) is an inherited disease that affects several body systems, including the immune system. ... Diagnosis of Ataxia-Telangiectasia. The diagnosis of A-T is usually based on common clinical features (ataxia, telangiectasia, ...
Ataxia. Cerebellar Ataxia. Telangiectasis. Ataxia Telangiectasia. Dyskinesias. Neurologic Manifestations. Nervous System ... Baclofen Treatment of Ataxia Telangiectasia. The safety and scientific validity of this study is the responsibility of the ... Genetics Home Reference related topics: VLDLR-associated cerebellar hypoplasia Ataxia-telangiectasia Autosomal recessive ... ways to measure the problems of ataxia and abnormal eye movement for future studies of medication in ataxia telangiectasia. ...
... in the May 1 issue of G&D lends new insight into the pathogenesis of neurodegeneration in Ataxia telangiectasia. ... Tags: Ataxia, Ataxia-Telangiectasia, Cancer, Cell, Cell Cycle, DNA, DNA Damage, Gene, Genetic, Genetics, Genomic, ... in the May 1 issue of G&D lends new insight into the pathogenesis of neurodegeneration in Ataxia telangiectasia.. Ataxia ... New insight into the pathogenesis of neurodegeneration in Ataxia telangiectasia. *Download PDF Copy ...
Discover smart, unique perspectives on Ataxia Telangiectasia and the topics that matter most to you like care coordination, ... Read stories about Ataxia Telangiectasia on Medium. ...
ataxia-telangiectasia;. ATM,. A-T-mutated;. PI 3-kinase,. phosphatidylinositol 3-kinase;. HO,. heme oxygenase. ... Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs. Carrolee Barlow, Phyllis A. Dennery, ... Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of ... Ataxia-telangiectasia (A-T) is an inherited disease causing progressive neurological dysfunction, especially in the cerebellum ...
This project is intended to produce a porcine model of ataxia-telangiectasia that will provide academic and industry ... DESCRIPTION (provided by applicant): Ataxia-telangiectasia (A-T) is a multi-systemic, recessively inherited disorder that ... ataxia-telangiectasia. This project is relevant to the NIHs mission because it will provide a resource to stimulate discovery ... It is characterized primarily by early onset cerebellar ataxia andtelangiectasia, from which the disease name is derived. In ...
See a picture of and learn about ataxia telangiectasia, a type of skin condition, in the eMedicineHealth Image Collection ... Picture of Ataxia Telangiectasia. Ataxia telangiectasia is a genetic condition that manifests in early childhood. It causes ... The photo depicts ocular telangiectasia, which is a reddening of the whites of the eyes caused by dilated blood vessels. Breaks ... cerebral ataxia (problems with balance and coordination), immune system abnormalities, and a predisposition to cancer. ...
It includes at least four distinct genetic entities: ataxia-telangiectasia, ataxia-telangiectasia-like disorder, and ataxia ... Anatomical context of Ataxia Telangiectasia. *ATM, the gene that is mutated in ataxia-telangiectasia, is associated with ... Chemical compound and disease context of Ataxia Telangiectasia. *Relationship of the ataxia-telangiectasia protein ATM to ... Biological context of Ataxia Telangiectasia. *ATM deficiency causes the genetic disorder ataxia-telangiectasia (A-T), ...
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  • Ataxia-telangiectasia happens when a change (mutation) in the gene that makes a protein called ATM protein. (kidshealth.org)
  • If parents know they carry the AT gene, or a family member has ataxia-telangiectasia, doctors can do genetic testing to diagnose it before a baby is born. (kidshealth.org)
  • Mutations in the ATM gene cause ataxia-telangiectasia. (medlineplus.gov)
  • The gene associated with A-T is ATM , meaning ataxia telangiectasia mutated. (cancer.net)
  • We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein. (pnas.org)
  • Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1% of the general population, also have an excess risk of cancer, particularly breast cancer in women. (medscape.com)
  • In addition, individuals with one ataxia telangiectasia gene (carriers) also appear to have an elevated risk for cancer. (rarediseases.org)
  • The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal regions containing doublestrand breaks. (acronymfinder.com)
  • Ataxia-telangiectasia group D complementing (ATDC) is a gene implicated in ataxia-telangiectasia. (wikipedia.org)
  • To examine mortality rates among persons carrying a mutated ataxia-telangiectasia gene. (nih.gov)
  • Gatti RA, Berkel I, Boder E, et al (1988) Localisation of an ataxia telangiectasia gene to chromosome 11q22-23. (springer.com)
  • The responsible gene in AT, ataxia-telangiectasia mutated (ATM), was discovered in 1995 by Savitsky et al. (bionity.com)
  • A-T is caused by recessive mutations in the ataxia telangiectasia mutated (ATM) gene. (news-medical.net)
  • All known cases are caused by mutations in the ATM (for ataxia-telangiectasia-mutated) gene ( 2 ), which encodes a protein similar to the phosphatidylinositol 3-kinase (PI 3-kinase) family of kinases ( 2 ). (pnas.org)
  • The gene that is mutated in ataxia-telangiectasia (A-T), ATM, is catalytically activated in response to DNA damage. (jneurosci.org)
  • Mutations in the ATM (Ataxia-Telangiectasia Mutated) gene are responsible for causing AT. (cags.org.ae)
  • Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are well-known single-gene disorders, which have similar cellular phenotypes, including chromosome instability, radioresistant DNA synthesis, and hypersensitivity to radiation. (springer.com)
  • The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. (springer.com)
  • A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 1q22-23. (springer.com)
  • A single ataxia telangiectasia gene with a product similar to PI-3 kinase. (springer.com)
  • Cancer rates were significantly higher in the group of blood relatives than in their spouses, specifically in the subgroup of 294 blood relatives who were known to be heterozygous for the ataxia-telangiectasia gene. (uni-bonn.de)
  • The ataxia-telangiectasia gene predisposes heterozygotes to cancer, particularly breast cancer in women. (uni-bonn.de)
  • Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. (ajnr.org)
  • Localization of an ataxia-telangiectasia gene to an approximately 500-kb interval on chromosome 11q23.1: linkage analysis of 176 families by an international consortium. (ajnr.org)
  • Germline mutations in the ATM gene cause the autosomal recessive neurological disease ataxia telangiectasia (A-T). The prevalence of A-T is ~1/40,000 - 1/100,000 affected individuals, with a carrier frequency of ~1/100. (cityofhope.org)
  • Diagnosis of ataxia-telangiectasia is confirmed by identifying mutations on both alleles of the gene for ATM protein. (merckmanuals.com)
  • The disease results from defects in the ataxia telangiectasia mutated (ATM) gene. (stlukes-stl.com)
  • Purpose: Studies of the association between ataxia telangiectasia-mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. (osti.gov)
  • Hypomorphic mutations of the MRE11 gene are the hallmark of the radiosensitive ataxia-telangiectasia-like disorder (ATLD). (sigmaaldrich.com)
  • A gene, ATM, that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. (sciencemag.org)
  • A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. (springermedizin.de)
  • A-T, alternatively known as Louis-Barr disease, refers to an autosomal-recessive cerebellar ataxia disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. (itbusinessnet.com)
  • In order to identify the human chromosome which carries a mutated gene in cells from a patient with the hereditary disorder ataxia telangiectasia belonging to complementation group D (AT-D), we performed chromosome transfer experiments via microcell fusion. (nii.ac.jp)
  • A-T is caused by defects in Ataxia-Telagiectasia Mutated (Atm) gene. (unina.it)
  • The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). (aacrjournals.org)
  • Inactivating mutations in the ataxia telangiectasia-mutated ( ATM ) gene lead to radiation hypersensitivity, defects in DNA damage checkpoint functions, and chromosomal instability ( 1 - 3 ). (aacrjournals.org)
  • More than 400 mutations in this large gene (62 exons spanning ∼150 kb) have been documented in ataxia telangiectasia (AT) patients, of which ∼70% are truncating mutations and 30% are missense mutations ( 5 - 8 ). (aacrjournals.org)
  • Ataxia telangiectasia is a recessive genetic condition, which means that in order for a child to have the disease, he or she will need to have two copies of the affected gene -- one from each parent. (emedtv.com)
  • People who have one normal copy and one altered copy of the ATM gene are carriers of ataxia telangiectasia. (emedtv.com)
  • The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. (cancer.gov)
  • ATR (ataxia telangiectasia and Rad3 related) is a protein-coding gene. (cancer.gov)
  • The gene responsible for ataxia telangiectasia, ATM, has been identified and ATM mutations have been found in all four complementation groups, suggesting a single AT gene (68). (alpfmedical.info)
  • Role of the ataxia-telangiectasia gene (ATM) in breast cancer. (freethesaurus.com)
  • Ataxia-telangiectasia-like disorder (ATLD) is caused by mutations in the MRE11/ MRE11A gene, which is involved in homologous recombination, telomere length maintenance, cell cycle checkpoint control and DNA double-strand break repair (Taylor et al. (preventiongenetics.com)
  • Defect in the DNA break repair gene AT M (Ataxia Telangiectasia Mutant). (blogspot.com)
  • Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. (meta.org)
  • A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. (uniprot.org)
  • Ataxia-telangiectasia (A-T) is an autosomal recessive, complex, multisystem disorder characterized by progressive neurologic impairment, cerebellar ataxia, variable immunodeficiency with susceptibility to sinopulmonary infections, impaired organ maturation, x-ray hypersensitivity, ocular and cutaneous telangiectasia (see image below), and a predisposition to malignancy. (medscape.com)
  • Ataxia-telangiectasia should be considered among the immunodeficiency diseases, cancer-prone genetic disorders, chromosomal instability syndromes, disorders with abnormal radiosensitivity, syndromes with possible DNA-repair/processing defects, and (as is now evident) the progeroid syndromes. (medscape.com)
  • The disorder is characterized by progressively impaired coordination of voluntary movements (ataxia), the development of reddish lesions of the skin and mucous membranes due to permanent widening of groups of blood vessels (telangiectasia), and impaired functioning of the immune system (i.e., cellular and humoral immunodeficiency), resulting in increased susceptibility to upper and lower respiratory infections (sinopulmonary infections). (rarediseases.org)
  • It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency, with defects in both cellular and humoral immunity. (nih.gov)
  • Ataxia-telangiectasia (AT) ( Boder-Sedgwick syndrome [1] or Louis-Bar syndrome ) is a primary immunodeficiency disorder that occurs in an estimated incidence of 1 in 40,000 to 1 in 300,000 births (Lederman, 2000). (bionity.com)
  • Ataxia telangiectasia (A-T) is a rare, genetic immunodeficiency disease that affects multiple organ systems and is characterized by neurodegeneration and cancer predisposition. (news-medical.net)
  • Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. (clinicaltrials.gov)
  • This report describes twin girls with typical features of ataxia-telangiectasia, including increased alpha-fetoprotein, radio-resistant DNA synthesis, characteristic chromosome abnormality, and immunodeficiency. (nih.gov)
  • Complementation was observed with patients in ataxia-telangiectasia complementation groups A, C, and E but not with the cell line from a patient with the Nijmegen breakage syndrome, in which patients have microcephaly, radio-resistant DNA synthesis, chromosome aberrations, and immunodeficiency but lack ataxia and telangiectasia. (nih.gov)
  • Diagnosis of the disease is made from a constellation of characteristic features, including cerebellar ataxia, oculomotor abnormalities, ocular and cutaneous telangiectasias, and immunoglobulin A, immunoglobulin E, or immunoglobulin G 2 immunodeficiency, with susceptibility to sinonasal and pulmonary infections and lymphoreticular malignancies (5-8) . (ajnr.org)
  • Ataxia Telangiectasia (AT) is a rare and progressive genetic disorder characterized by primary immunodeficiency and a resultant degradation of the nervous system. (cags.org.ae)
  • Immunodeficiency and infections in ataxia-telangiectasia. (ajnr.org)
  • Ataxia-telangiectasia is an autosomal-recessive primary immunodeficiency disorder that involves combined humoral and cellular deficiencies . (merckmanuals.com)
  • Ataxia telangiectasia is a rare autosomal recessive disorder characterized by unsteady gait (ataxia), telangiectasia of eye and skin and a variable immunodeficiency disorder (both cellular and humoral) and a high incidence of malignancy. (pediatriconcall.com)
  • In contrast to AT, ATLD patients lack key clinical features, such as telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed. (nii.ac.jp)
  • Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. (springermedizin.de)
  • Ataxia-Telangiectasia (A-T) is a recessive hereditary syndrome characterized by cerebellar degeneration, telangiectasia, precocious aging, immunodeficiency, cancer predisposition and insulin-resistant diabetes. (unina.it)
  • Ataxia telangiectasia (A-T) is a rare devastating human recessive disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. (ichgcp.net)
  • Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. (wikipedia.org)
  • The following symptoms or problems are either common or important features of A-T: Ataxia (difficulty with control of movement) that is apparent early but worsens in school to pre-teen years Oculomotor apraxia (difficulty with coordination of head and eye movement when shifting gaze from one place to the next) Involuntary movements Telangiectasia (dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. (wikipedia.org)
  • Prominent blood vessels (telangiectasia) over the white (sclera) of the eyes usually occur by the age of 5-8 years, but sometimes appear later or not at all. (wikipedia.org)
  • Red marks called telangiectasias are caused by dilated capillaries, meaning tiny blood vessels, and may appear on the skin and eyes as people get older. (cancer.net)
  • The telangiectasias (visible dilated blood vessels) usually begin in the eyes (the eyes look "bloodshot") between three and six years of age, although they can occur earlier. (rarediseases.org)
  • Dilated and corkscrew-shaped blood vessels (telangiectasias) cause the whites of the eyes to look bloodshot or as if there is pink eye (conjunctivitis) or an allergy. (primaryimmune.org)
  • The photo depicts ocular telangiectasia, which is a reddening of the whites of the eyes caused by dilated blood vessels. (emedicinehealth.com)
  • Telangiectasias are enlarged blood vessels (capillaries) just below the surface of the skin. (mountsinai.org)
  • The most obvious features of A-T are the loss of balance and coordination (ataxia), and the appearance of clusters of blood vessels on the whites of the eye (telangiectasia) that make them appear bloodshot. (atcp.org)
  • This is a recessive inherited disorder with many manifestations, most starting in early childhood including ataxic (drunken like) walking, peculiar eye tracking motions which inhibit learning, telangiectasia which are dilated blood vessels especially prominent on the eyes but also in sun exposed areas, and many other problems. (healthtap.com)
  • Ataxia is usually noted early in life, and a key feature is the presence of dilated blood vessels visible in the sclerae of the eyes and on the cheeks and ears. (oup.com)
  • Ataxia telangiectasia is a neurodegenerative, rare, inherited disease which causes severe disability because of poor coordination and telangiectasia to small dilated blood vessels, both symptoms of the disease. (healthician.org)
  • We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). (bmj.com)
  • What is the treatment of Ataxia Telangiectasia? (pediatriconcall.com)
  • OXFORD, UK / ACCESSWIRE / March 13, 2019 / IntraBio Inc., a late-stage biopharmaceutical company, today announced that the US Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) Application for Clinical Trial IB1001-203 with its lead compound (IB1001) for the treatment of Ataxia-Telangiectasia (A-T). (itbusinessnet.com)
  • The A-T Children's Project (Ataxia Telangiectasia Children's Project) (ATCP) is a national, non-profit organization that was established in 1993. (rarediseases.org)
  • Hecht F, McKaw K (1982) Ataxia telangiectasia - genetics and heterogeneity. (springer.com)
  • Ataxia-telangiectasia (A-T) is a rare, inherited disease. (medlineplus.gov)
  • Ataxia telangiectasia (A-T) is a rare, inherited disease that affects several organs and systems, including the nervous and the immune systems. (hopkinsmedicine.org)
  • Ataxia-Telangiectasia (A-T) is an inherited disease that affects several body systems, including the immune system. (primaryimmune.org)
  • Ataxia-telangiectasia (A-T) is an inherited disease causing progressive neurological dysfunction, especially in the cerebellum ( 1 ). (pnas.org)
  • Ataxia-telangiectasia combines central nervous system disease with an oculocutaneous anomaly, fulfilling the criteria for classification within the phacomatoses group of diseases. (medscape.com)
  • Telangiectasia can be a symptom of scleroderma or other systemic diseases. (mountsinai.org)
  • Diseases associated with ATR include cutaneous telangiectasia and cancer syndrome, familial, and chronic active epstein-barr virus infection. (cancer.gov)
  • To learn how ataxia-telangiectasia runs in families, talk to a genetic counselor . (kidshealth.org)
  • Ataxia-telangiectasia (AT) is an autosomal recessive genetic disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, and recurrent respiratory and sinus infections. (medscape.com)
  • Ataxia telangiectasia (AT) is a complex genetic neurodegenerative disorder that may become apparent during infancy or early childhood. (rarediseases.org)
  • Ataxia-telangiectasia (A-T) is a rare, genetic neurological disorder that progressively affects various systems in the body. (encyclopedia.com)
  • Huang PC, Sheridan RB (1981) Genetic and biochemical studies with ataxia telangiectasia. (springer.com)
  • Jaspers NGJ, Bootsma D (1982) Genetic heterogeneity in ataxia telangiectasia studied by cell fusion. (springer.com)
  • Ataxia telangiectasia is a genetic condition that manifests in early childhood. (emedicinehealth.com)
  • Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by gait disorders, neuromotor dysfunction, eye abnormalities and immune deficiency. (clinicaltrials.gov)
  • Ataxia Telangiectasia is a genetic problem and if an individual has a child with Ataxia Telangiectasia, there is 25% chance of recurrence in the next child. (pediatriconcall.com)
  • Ataxia telangiectasia is a genetic condition with no cure. (healthtap.com)
  • Ataxia telangiectasia is caused by a genetic mutation. (healthtap.com)
  • Is hemorrhagic telangiectasia (hht) a genetic disease? (healthtap.com)
  • Ataxia-telangiectasia (A-T), also called Louis-Bar syndrome, is a rare, genetic neurological disorder of childhood that progressively destroys part of the motor control area of the brain, leading to a lack of balance and coordination. (thefreedictionary.com)
  • What Are the Signs & Symptoms of Ataxia-Telangiectasia? (kidshealth.org)
  • Therefore, ataxia-telangiectasia symptoms include all the possible consequences of the perturbations in DNA damage response (DDR). (medscape.com)
  • The diagnosis of A-T may not be made until the preschool years when the neurologic symptoms of impaired gait, hand coordination, speech and eye movement appear or worsen, and the telangiectasia first appear. (wikipedia.org)
  • Atm-deficient mice then exhibit many of the same symptoms found in ataxia-telangiectasia patients and in cells derived from them. (pnas.org)
  • Ataxia-telangiectasia (AT) is a human autosomal recessive disorder characterized by a wide variety of progressive clinical symptoms (for review, see ref. 1 ). (pnas.org)
  • The main symptoms of AT include cerebellar ataxia, oculocutaneous telangiectasias, acute sensitivity to ionizing radiation, thymic degeneration, immunodeficiencies and subsequent recurrent sinopulmonary infections, high incidences of lymphoma and leukemia, growth retardation, incomplete sexual maturation, and progeric changes to hair and skin. (pnas.org)
  • Although there is much variability in A-T symptoms among patients, the signs of A-T almost always include the appearance of ataxia between the ages of two and five. (encyclopedia.com)
  • Ataxia-telangiectasia-like disorder (ATLD) is a rare autosomal recessive disorder, and has symptoms similar to ataxia-telangiectasia (AT). (nii.ac.jp)
  • Ataxia telangiectasia (AT) is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. (oup.com)
  • The DelveInsight Ataxia Telangiectasia (AT) market report gives a thorough understanding of the Ataxia Telangiectasia (AT) by including details such as disease definition, symptoms, causes, pathophysiology, diagnosis and treatment. (delveinsight.com)
  • Ataxia-telangiectasia (A-T) [1] is a progressive neurodegenerative disorder characterized by a wide range of clinical manifestations, including cerebellar ataxia, conjunctival telangiectases, recurrent sinopulmonary infections, radiosensitivity, and increased cancer susceptibility (1). (acronymfinder.com)
  • Ataxia Telangiectasia [ATM]: Autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. (jewishgeneticdiseases.org)
  • Children with ataxia-telangiectasia (uh-TAK-see-uh tel-an-jee-ek-TAY-zhuh) have uncoordinated movements that get worse over time. (kidshealth.org)
  • Doctors might suspect ataxia-telangiectasia when a child has an unsteady walk, unusual eye or body movements, and many infections or telangiectasias. (kidshealth.org)
  • This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood, usually before age 5. (medlineplus.gov)
  • Ataxia refers to uncoordinated movements, such as walking. (mountsinai.org)
  • Ataxia means movements without coordination. (healthtap.com)
  • Progressive ataxia is generally the first symptom, followed by choreiform movements (in approx 90% of patients) and conjunctival telangiectasias, which usually appear between 3 and 5 yr of age. (alpfmedical.info)
  • It is a progressive difficulty with movements coordination (ataxia) beginning in early childhood, generally before age 5. (healthician.org)
  • This autosomal recessive disorder, with a birth incidence of about 1 in 300,000, is characterized by the development of cerebellar ataxia in the first decade, along with choreoathetosis, dysarthria, and abnormalities of ocular movements. (genomicmedicineuk.com)
  • Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal degeneration, immune dysfunction, premature ageing and increased cancer risk. (uptodate.com)
  • Mutation of ATM occurs in the human autosomal recessive disorder ataxia-telangiectasia, which is characterized by hypersensitivity to ionizing radiation and a failure of cells to arrest the cell cycle after the induction of DNA double-strand breaks. (aacrjournals.org)
  • Ataxia Telangiectasia and Rad3-related (ATR) or FRAP-related protein-1 (FRP1) is a 2644 amino acid protein kinase, located on chromosome 3q23 (Cimprich et al. (springer.com)
  • Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers. (springer.com)
  • Nam EA, Zhao R, Glick GG, Bansbach CE, Friedman DB, Cortez D. Thr-1989 phosphorylation is a marker of active ataxia telangiectasia-mutated and Rad3-related (ATR) kinase. (springer.com)
  • Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. (uptodate.com)
  • The primary transducer of the cellular response to the double-strand break, a highly cytotoxic DNA lesion, is the nuclear protein kinase ataxia telangiectasia (A-T) mutated (ATM), which phosphorylates numerous effectors that play key roles in the damage response pathways. (jneurosci.org)
  • Among the members of this family are ataxia-telangiectasia (A-T) mutated (ATM) and the DNA-dependent protein kinase (DNA-PK), which respond primarily to DSBs that are involved in the nonhomologous end-joining pathway of DSB repair, and ataxia telangiectasia Rad 3-related (ATR), which responds primarily to UV damage and stalled replication forks but also shares with ATM substrates in the DSB response pathway. (jneurosci.org)
  • The aim of the study reported here was to further investigate the potential effect of ataxia-telangiectasia mutated (ATM) kinase-dependent hyperphosphorylation of checkpoint kinase-2 (Chk2) on radiosensitivity enhanced by oligodeoxynucleotide 7909 containing CpG motifs (CpG ODN7909) in human lung adenocarcinoma A549 cells. (dovepress.com)
  • However, following ATM kinase inhibition using a specific ATM inhibitor, we observed a significant increase in ATM and ataxia-telangiectasia and Rad3 related transcription. (royalsocietypublishing.org)
  • The pathway is negatively controlled by the protein degradation system that includes the Mdm2 E3 ligase and is positively activated by the ataxia-telangiectasia mutated (ATM) protein kinase. (royalsocietypublishing.org)
  • DDR pathways are initiated by phosphoinositide 3-kinase-like kinase family (PIKK) members, including ATM and ataxia-telangiectasia and Rad3 related (ATR), which recognize distinct types of DNA damage. (royalsocietypublishing.org)
  • Additional studies revealed that GSE causes DNA damage-induced activation of ataxia telangiectasia mutated kinase and Chk2, as well as p53 Ser 15 phosphorylation and its translocation to mitochondria, suggesting this to be an additional mechanism for apoptosis induction. (aacrjournals.org)
  • The aim of the present study was to elucidate the effects of ataxia telangiectasia mutated (ATM) kinase on the regulation of the extrinsic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2/DR5-mediated death pathway in human melanoma cells. (columbia.edu)
  • Clonogenic assays demonstrated a significant sensitization in NK314-treated cells deficient in DNA-dependent protein kinase (DNA-PK) catalytic subunit, Ku80, ataxia telangiectasia mutated (ATM), BRCA2, or XRCC3 compared with wild-type cells, indicating that both nonhomologous end-joining and homologous recombination DNA repair pathways contribute to cell survival. (aspetjournals.org)
  • Ataxia telangiectasia and Rad3-related kinase (ATR), a member of the phosphatidylinositol-3-related protein kinases (PIKK), represents a candidate target for achieving this goal. (eurekaselect.com)
  • Ataxia telangiectasia is a multisystem disease characterized by cerebellar ataxia, oculomucocutaneous telangiectasias, and susceptibility to certain infections and neoplastic processes. (ajnr.org)
  • ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. (freethesaurus.com)
  • A gap of some 15 years occurred before the next report in 1941 by Louis-Bar, who described progressive cerebellar ataxia and cutaneous telangiectasia in a Belgian child. (medscape.com)
  • Ataxia-telangiectasia can also be classified among the neurocutaneous syndromes, although not among the phakomatoses as originally proposed, because the vascular and cutaneous lesions of ataxia-telangiectasia are not congenital nevi but develop in the course of the disease as a progeric manifestation. (medscape.com)
  • Oculocutaneous telangiectasia develops in childhood (often after ataxia is apparent) and then spreads to involve other exposed cutaneous areas. (genomicmedicineuk.com)
  • Syllaba and Henner first published descriptions of patients with ataxia-telangiectasia in 1926. (medscape.com)
  • [ 11 ] The authors analyzed the production of antibodies to polysaccharide antigens in patients with ataxia-telangiectasia and found that the levels of immunoglobulin G (IgG) antibodies to serotypes 1, 3, 5, 6B, 9V, and 14 of Streptococcus pneumoniae before and after immunization with 23-valent polysaccharide vaccine were significantly lower than in a healthy population. (medscape.com)
  • The cause of death in more than 50% of patients with ataxia-telangiectasia is recurrent respiratory infections. (medscape.com)
  • Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. (medscape.com)
  • The mean age of patients with ataxia-telangiectasia at the time of presentation is 2.5-7 years. (medscape.com)
  • More than 50% of patients with ataxia-telangiectasia die of recurrent respiratory infections, and many of the remainder develop malignancies, such as leukemia or lymphomas. (medscape.com)
  • 405 grandparents of patients with ataxia-telangiectasia. (nih.gov)
  • immunogenicity in patients with ataxia-telangiectasia. (uio.no)
  • Cancer incidence and mortality, mortality from ischemic heart disease, and mortality from all causes were compared prospectively for a mean of 6.4 years in 1599 adult blood relatives of patients with ataxia-telangiectasia and 821 of their spouses, who served as controls, in 161 families affected by ataxia-telangiectasia. (uni-bonn.de)
  • Cancer in patients with ataxia-telangiectasia and in their relatives in the Nordic countries. (ajnr.org)
  • Treatment with prophylactic antibiotics or immune globulin may help patients with ataxia-telangiectasia. (merckmanuals.com)
  • To test whether transrearrangements result from chromosomal rearrangements with breakpoints at the sites of Ag receptor genes, PCR was performed on the DNA of PBL from patients with ataxia telangiectasia, a disorder in which circulating lymphocytes often have numerous karyotypic abnormalities with breakpoints at the cytogenetic positions of these genes. (jimmunol.org)
  • In conclusion, when assessing patients with ataxia of unknown cause, ATLD should be considered, and the gonadal state and peripheral blood smear samples evaluated. (nii.ac.jp)
  • The effects of weekly doses of transfer factor in four patients with ataxia--telangiectasia were investigated following a total course of 2 months therapy. (curehunter.com)
  • The late appearance of telangiectasia may be a barrier to the diagnosis. (wikipedia.org)
  • The absence of telangiectasia does not exclude the diagnosis of A-T. Potentially a cosmetic problem, the ocular telangiectasia do not bleed or itch, though they are sometimes misdiagnosed as chronic conjunctivitis. (wikipedia.org)
  • The simultaneous absence of telangiectasias and of other nonneurological manifestations made ataxia-telangiectasia an unlikely diagnosis. (uptodate.com)
  • DIAGNOSIS Ataxia-telangiectasia DISCUSSION Ataxia-telangiectasia (AT), also known as Louis-Bar syndrome, is a hereditary autosomal recessive progressive multisystem disease. (acronymfinder.com)
  • Ataxia telangiectasia like disorder (ATLD) is an extremely rare condition which could be considered as a differential diagnosis to AT. (bionity.com)
  • The diagnosis of A-T is often difficult to make when ataxia is the only symptom present. (primaryimmune.org)
  • Telangiectasias eventually occur in most patients with A-T but do not occur in all patients with A-T and are only rarely present in infants and very young children, another reason that the diagnosis of A-T may be delayed until school age. (primaryimmune.org)
  • How is the diagnosis of Ataxia Telangiectasia made? (pediatriconcall.com)
  • The diagnosis of Ataxia Telangiectasia is usually based on characteristic clinical findings. (pediatriconcall.com)
  • The diagnosis of A-T syndrome is established in patients over one year of age who show ataxia with a serum level of alpha fetoproteins (AFP) more than twice the upper limit of normal. (pediatriconcall.com)
  • This aspect can be helpful in diagnosis of AT in young children with cerebellar ataxia. (arizona.edu)
  • differential diagnosis compared with AT-LD (ataxia Telangiectasia-like disorder), AOA1 and AOA2 (ataxias with oculomotor apraxia type 1 and 2 (AOA1, AOA2) is primarily done in the laboratory on the basis of a multiple Western blots done with the specific antibodies. (clinicalpainadvisor.com)
  • Ocular manifestations of ataxia-telangiectasia. (nih.gov)
  • To report the manifestations of ataxia-telangiectasia (A-T) on the ocular sensory and motor systems. (nih.gov)
  • Static ataxia (disruption of balance when the person is standing) and locomotor ataxia (actual disruption of the coordination of movement) are distinguished according to clinical manifestations. (thefreedictionary.com)
  • Frontal ataxia, which occurs with the disruption of frontal-cerebellar pathways, is similar to cerebellar ataxia in its manifestations. (thefreedictionary.com)
  • Biton S, Barzilai A, Shiloh Y. The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle. (medlineplus.gov)
  • Ataxia-telangiectasia, an evolving phenotype. (medlineplus.gov)
  • 1996) and others have reported families with a milder clinical and cellular phenotype due to certain ataxia-telangiectasia mutations (Sariozzi et al. (genomicmedicineuk.com)
  • The first case described in the literature was a 9-year-old child with progressive cerebellar ataxia and bilateral oculocutaneous telangiectasia reported in 1941 by Madame Louis-Bar. (medscape.com)
  • a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. (medscape.com)
  • AT is characterized by progressive cerebellar ataxia , oculocutaneous telangiectasia , progressive cerebellar dysfunction, and recurrent sinopulmonary infections secondary to progressive immunological and neurological dysfunction. (bionity.com)
  • Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. (uptodate.com)
  • Ataxia-telangiectasia is a rare inherited disorder that affects the nervous system, immune system, and other body systems. (medlineplus.gov)
  • People with ataxia-telangiectasia often have a weakened immune system, and many develop chronic lung infections. (medlineplus.gov)
  • For these patients, the combination of a weakened immune system and progressive ataxia can ultimately lead to pneumonia as a cause of death. (encyclopedia.com)
  • It causes cerebral ataxia (problems with balance and coordination), immune system abnormalities, and a predisposition to cancer . (emedicinehealth.com)
  • The life expectancy of people with ataxia-telangiectasia varies greatly, but affected individuals typically live into early adulthood. (medlineplus.gov)
  • In people with ataxia telangiectasia, the ATM protein is missing or defective. (emedtv.com)
  • Mortality rates among carriers of ataxia-telangiectasia mutant alleles. (nih.gov)
  • Children with ataxia-telangiectasia are cared for by a health care team. (kidshealth.org)
  • Children with ataxia-telangiectasia should have psychologic counseling as they age because of the great disparity between chronological age and mental age in tests involving visual motor coordination. (medscape.com)
  • We describe herewith 3 children with ataxia telangiectasia (AT) who presented to us with recurrent chest infections. (pediatriconcall.com)
  • The protein ATM when mutated is responsible for Ataxia-telangiectasia, which acts upstream of the MRN complex and is responsible for MRN activation through phosphorylation. (preventiongenetics.com)
  • The level of this protein is normally increased in the bloodstream of pregnant women, but it is unknown why individuals with ataxia-telangiectasia have elevated AFP or what effects it has in these individuals. (medlineplus.gov)
  • As has been shown by Guerra-Maranhao et al, ataxia-telangiectasia patients are at high risk of having impaired responses to infection with pneumococci, which may be one of the causes of recurrent sinopulmonary infections in these patients. (medscape.com)
  • Ataxia can be associated with infections, injuries, or degenerative changes in the central nervous system. (healthtap.com)
  • it causes progressive cerebellar ataxia, oculocutaneous telangiectasias, and recurrent sinopulmonary infections. (merckmanuals.com)
  • The third patient was diagnosed at 1 year of age with ataxia and recurrent chest infections. (pediatriconcall.com)
  • Mutations at the ataxia-telangiectasia locus cause a distinctive autosomal recessive syndrome in homozygotes and predispose heterozygotes to cancer and ischemic heart disease. (nih.gov)
  • Arlett CF, Priestley A (1985) An assessment of the radiosensitivity of ataxia telangiectasia heterozygotes. (springer.com)
  • Cellular sensitivity of human skin fibroblast strains from three healthy donors, eight ataxia-telangiectasia (A-T) patients belonging to six sibships, and two A-T heterozygotes to the lethal action of the antitumor antibiotic neocarzinostatin was tested, using colony-forming ability as the criterion for survival. (aacrjournals.org)
  • Heterogeneity in the clastogenic response to x-rays in lymphocytes from Ataxia-telangiectasia heterozygotes and controls. (cdc.gov)
  • A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. (cdc.gov)
  • Identification of ataxia telangiectasia heterozygotes by flow cytometric analysis of X-ray damage. (semanticscholar.org)
  • Flow cytometry was used to identify heterozygotes for the autosomal recessive DNA-repair deficiency disease ataxia telangiectasia (AT). (semanticscholar.org)
  • ATLD patients are very similar to AT patients in showing a progressive cerebellar ataxia, hypersensitivity to ionising radiation and genomic instability. (bionity.com)
  • AT M is inactivated in ataxia telangiectasia-->hypersensitivity to x-rays and predisposition to lymphomas. (blogspot.com)
  • Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis. (springer.com)
  • These findings further underscore the interconnection between ATM activity and MRN function, which rationalizes the clinical similarity between ataxia-telangiectasia (A-T) and ATLD. (sigmaaldrich.com)
  • Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje cells. (pnas.org)
  • Ataxia-telangiectasia: an inherited disorder of ionizing-radiation sensitivity in man. (springer.com)
  • Diagnostic or occupational exposure to ionizing radiation probably increases the risk of breast cancer in women heterozygous for ataxia-telangiectasia. (uni-bonn.de)
  • By contrast, KU-55933 did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage. (aacrjournals.org)
  • The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells. (asm.org)
  • Although the neurological signs were indistinguishable from those of ataxia-telangiectasia, the onset tended to be later and none of the patients had evidence of multisystemic involvement. (uptodate.com)
  • The work provides new insights into mechanisms of how the body fixes environmentally induced DNA damage and into the deadly neurological disease ataxia-telangiectasia (A-T), said senior author Christopher Bakkenist, assistant professor of radiation oncology, pharmacology and chemical biology at UPCI and the School of Medicine. (acronymfinder.com)
  • Can my neurological disease of spinocelebar ataxia cause irritable bowel syndrome with. (healthtap.com)
  • They presented with late onset cerebellar degeneration slowly progressing until puberty and absence of telangiectasias, and were cancer-free. (sigmaaldrich.com)
  • Ataxia-telangiectasia (A-T) is a hereditary condition characterized by progressive neurologic problems that lead to difficulty walking and an increased risk of developing various types of cancer. (cancer.net)
  • Living with hht (hereditary hemorrhagic telangiectasia), how to make things better? (healthtap.com)
  • There is no cure for hht hereditary hemorrhagic telangiectasia . (healthtap.com)
  • How do people treat hereditary hemorrhagic telangiectasia? (healthtap.com)
  • Hereditary hemorrhagic telangiectasia (hht). (healthtap.com)
  • One basic defect associated with the malady is the abnormal sensitivity of ataxia-telangiectasia cells to x-rays and certain radiomimetic chemicals but not to ultraviolet irradiation, which leads to chromosome and chromatid breaks. (medscape.com)
  • Ataxia-Telangiectasia A-T is a neurodegenerative disorder of the cerebellum, manifesting with ataxia, as well as extrapyramidal features. (clinicaltrials.gov)
  • Ataxia-telangiectasia, a neurodegenerative disorder. (ajnr.org)
  • Carriers of mutations at the ataxia-telangiectasia locus, who make up 1.4% to 2% of the general population, have a higher mortality rate and an earlier age at death from cancer and ischemic heart disease than noncarriers. (nih.gov)
  • The patient had a history of gait ataxia since age 4 years and was diagnosed with ataxia telangiectasia at age 7 after developing ocular telangiectasias. (ajnr.org)
  • gait ataxia and lymphopenia, especially of CD4, and immunoglobulin deficiencies, mainly of IgA and/or IgG subclasses. (pediatriconcall.com)
  • Truncal ataxia (oscillations of the trunk) may be evident at the 5th-6th months of life, while gait ataxia appears when the affected child starts to walk, with frequent falls. (clinicalpainadvisor.com)
  • [ 3 ] They observed progressive choreoathetosis and ocular telangiectasia in 3 members of a single family. (medscape.com)
  • We report 14 patients with a slowly progressive syndrome featuring ataxia, choreoathetosis, and ocular motor apraxia in both the horizontal and vertical planes. (uptodate.com)
  • Ataxia-telangiectasia can best be classified, according to its major clinical and pathologic features, as a predominantly cerebellar form of spinocerebellar degeneration, which is transmitted as an autosomal recessive trait and evolves ultimately to include motor neuron disease, with spinal muscular atrophy and peripheral neuropathy. (medscape.com)
  • Ataxia-telangiectasia (AT or A-T), also referred to as ataxia-telangiectasia syndrome or Louis-Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. (wikipedia.org)
  • Initially known as the Louis-Bar syndrome, the term ataxia-telangiectasia was introduced in 1958 by Boder et al, who recorded the clinical features and recognized the familial incidence proposing an autosomal recessive mode of inheritance for the disease. (medscape.com)
  • Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. (medscape.com)
  • The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first described as a separate disease entity 40 years ago. (nih.gov)
  • These two features demonstrate that ataxia telangiectasia may not always be an autosomal recessive condition. (springer.com)
  • Ataxia telangiectasia is inherited as an autosomal recessive trait with an incidence of one in 20000 to 100000 births. (ajnr.org)
  • Ataxia telangiectasia (AT) is an autosomal recessive disorder that affects 1/40,000 to 1/100,000 individuals. (alpfmedical.info)
  • Ataxia Telangiectasia is inherited in autosomal recessive manner, which means that two healthy parents, both carriers of one ATM mutation, have at each pregnancy a 25% risk of giving birth to an affected child. (clinicalpainadvisor.com)
  • Publications] kenshi komatsu: 'Restoration of radiation resistance in ataxia telangiectasia cells by the introduction of normal human chromosome 11' Mutation Research. (nii.ac.jp)
  • Publications] Seiji Kodama: 'Suppression of X-ray-induced chromosome aberrations in atataxia telangiectasia cells by introducting normal human chromosomell' Mutation Research. (nii.ac.jp)
  • Clusters of blood vessel (telangiectasia) usually appear on the whites of the eyes by the time the child is five to eight years old. (atcp.org)
  • 2017. https://www.tabers.com/tabersonline/view/Tabers-Dictionary/740738/all/ataxia_telangiectasia. (tabers.com)
  • The Ataxia Telangiectasia (AT) market report provides current treatment practices, emerging drugs, Ataxia Telangiectasia (AT) market share of the individual therapies, current and forecasted Ataxia Telangiectasia (AT) market Size from 2017 to 2030 segmented by seven major markets. (delveinsight.com)
  • The disease epidemiology covered in the report provides historical as well as forecasted Ataxia Telangiectasia (AT) epidemiology scenario in the 7MM covering the United States, EU5 countries (Germany, Spain, Italy, France, and the United Kingdom), and Japan from 2017 to 2030. (delveinsight.com)
  • The patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive impairment, writing dystonia, hypergonadotropic hypogonadism with primary amenorrhea, and hypersegmented neutrophils. (nii.ac.jp)
  • The onset of cerebellar ataxia (unsteadiness and lack of coordination) marks the beginning of progressive degeneration of the cerebellum , the part of the brain responsible for motor control (movement). (encyclopedia.com)
  • It is characterized primarily by early onset cerebellar ataxia andtelangiectasia, from which the disease name is derived. (sbir.gov)
  • Could I be suffering from either early onset Parkinson's or ataxia telangiectasia? (healthtap.com)
  • The latter is suggested by an earlier onset of signs, the lack of cerebellar atrophy, and the absence of ataxia and ocular telangiectases on initial presentation. (arizona.edu)
  • Alpha fetoprotein is increasing with age in Ataxia-Telangiectasia Eur J Paediatr Neurol. (uio.no)
  • In those with AT, progressive ataxia typically develops during infancy and may initially be characterized by abnormal swaying of the head and trunk. (rarediseases.org)
  • This research is being done to find out if Baclofen, a medicine that is often used for the treatment of abnormal stiffness, might also be useful to treat some of the neurologic problems caused by ataxia telangiectasia (A-T). The investigators also want to find out if there are better ways to measure the problems of ataxia and abnormal eye movement for future studies of medication in ataxia telangiectasia. (clinicaltrials.gov)
  • She was dysarthric, had an abnormal gait and bilateral limb ataxia. (cags.org.ae)
  • The name is a combination of two recognized abnormalities: ataxia (lack of muscle control) and telangiectasia (abnormal dilatation of capillary vessels that often result in tumors and red skin lesions ). (thefreedictionary.com)
  • She had bilateral conjunctival telangiectasias, bilateral foot drop, and no deep tendon reflex at the ankles. (ajnr.org)
  • Patients present in early childhood with progressive cerebellar ataxia and later develop conjunctival telangiectases, other progressive neurologic degeneration, sinopulmonary infection, and malignancies. (jewishgeneticdiseases.org)
  • The true incidence of ataxia-telangiectasia is unknown. (medscape.com)
  • The incidence of ataxia telangiectasia in the 79 sibs of index cases was 1 in 7. (springer.com)
  • The incidence of ataxia-telangiectasia is about 1 case in 100,000 births. (freethesaurus.com)
  • Progressive cerebellar ataxia usually becomes clinically apparent when the child begins to walk. (medscape.com)
  • Ataxia Telangiectasia is a progressive degenerative disease which affects various systems of the body. (pediatriconcall.com)
  • The ataxia is progressive and often begins as truncal unsteadiness with limbs involved later. (arizona.edu)
  • Like many genetically inherited ataxias, A-T is a disabling, progressive syndrome that severely impairs motor function and quality of life and becomes more disabling over the course of the disease. (itbusinessnet.com)
  • Children with A-T may begin staggering and appear unsteady (called ataxia) shortly after learning to walk. (cancer.net)
  • A-T is suspected whenever a child develops signs of ataxia, meaning unsteady walking. (cancer.net)
  • She was diagnosed with A-T at 7 years old due to unsteady gait, telangiectasia in eye and skin. (pediatriconcall.com)