Mutation, Missense: 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)DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Pedigree: 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.Mutation: 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.Molecular Sequence Data: 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.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Homozygote: An individual in which both alleles at a given locus are identical.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Consanguinity: The magnitude of INBREEDING in humans.Syndrome: A characteristic symptom complex.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Abnormalities, MultipleGenetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Genetic Diseases, X-Linked: Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Mental Retardation, X-Linked: A class of genetic disorders resulting in INTELLECTUAL DISABILITY that is associated either with mutations of GENES located on the X CHROMOSOME or aberrations in the structure of the X chromosome (SEX CHROMOSOME ABERRATIONS).Genetic Variation: Genotypic differences observed among individuals in a population.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)DNA-Binding Proteins: 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.Suppression, Genetic: Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Eye ProteinsGenes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Hearing Loss, Sensorineural: Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.Blepharophimosis: The abnormal narrowness of the palpebral fissure in the horizontal direction caused by the lateral displacement of the medial canthi of the eyelids. (Dorland, 27th ed)Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, FOCAL DERMAL HYPOPLASIA, and aplasia cutis congenita.Cerebellar Ataxia: 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)RNA Splice Sites: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.Aniridia: A congenital abnormality in which there is only a rudimentary iris. This is due to the failure of the optic cup to grow. Aniridia also occurs in a hereditary form, usually autosomal dominant.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.DNA: 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).Heterozygote Detection: Identification of genetic carriers for a given trait.Gene Deletion: 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.Gonadal Dysgenesis, 46,XY: Defects in the SEX DETERMINATION PROCESS in 46, XY individuals that result in abnormal gonadal development and deficiencies in TESTOSTERONE and subsequently ANTIMULLERIAN HORMONE or other factors required for normal male sex development. This leads to the development of female phenotypes (male to female sex reversal), normal to tall stature, and bilateral streak or dysgenic gonads which are susceptible to GONADAL TISSUE NEOPLASMS. An XY gonadal dysgenesis is associated with structural abnormalities on the Y CHROMOSOME, a mutation in the GENE, SRY, or a mutation in other autosomal genes that are involved in sex determination.Protein Binding: 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.Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)Intellectual Disability: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)Facies: The appearance of the face that is often characteristic of a disease or pathological condition, as the elfin facies of WILLIAMS SYNDROME or the mongoloid facies of DOWN SYNDROME. (Random House Unabridged Dictionary, 2d ed)Family: A social group consisting of parents or parent substitutes and children.Proteins: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Nuclear Proteins: 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.Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Deafness: A general term for the complete loss of the ability to hear from both ears.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.Osteochondrodysplasias: Abnormal development of cartilage and bone.Afibrinogenemia: A deficiency or absence of FIBRINOGEN in the blood.Tumor Suppressor Proteins: 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.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.BRCA1 Protein: 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)Microphthalmos: Congenital or developmental anomaly in which the eyeballs are abnormally small.Noonan Syndrome: A genetically heterogeneous, multifaceted disorder characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, CRYPTORCHIDISM, multiple cardiac abnormalities (most commonly including PULMONARY VALVE STENOSIS), and some degree of INTELLECTUAL DISABILITY. The phenotype bears similarities to that of TURNER SYNDROME that occurs only in females and has its basis in a 45, X karyotype abnormality. Noonan syndrome occurs in both males and females with a normal karyotype (46,XX and 46,XY). Mutations in a several genes (PTPN11, KRAS, SOS1, NF1 and RAF1) have been associated the the NS phenotype. Mutations in PTPN11 are the most common. LEOPARD SYNDROME, a disorder that has clinical features overlapping those of Noonan Syndrome, is also due to mutations in PTPN11. In addition, there is overlap with the syndrome called neurofibromatosis-Noonan syndrome due to mutations in NF1.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.Amino Acid Metabolism, Inborn Errors: Disorders affecting amino acid metabolism. The majority of these disorders are inherited and present in the neonatal period with metabolic disturbances (e.g., ACIDOSIS) and neurologic manifestations. They are present at birth, although they may not become symptomatic until later in life.Synostosis: A union between adjacent bones or parts of a single bone formed by osseous material, such as ossified connecting cartilage or fibrous tissue. (Dorland, 27th ed)MutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Neoplastic Syndromes, Hereditary: The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.X Chromosome: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.Cardiomyopathy, Hypertrophic: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).Syndactyly: A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.Cataract: Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Hypotrichosis: Presence of less than the normal amount of hair. (Dorland, 27th ed)Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Hyperlipoproteinemia Type I: An inherited condition due to a deficiency of either LIPOPROTEIN LIPASE or APOLIPOPROTEIN C-II (a lipase-activating protein). The lack of lipase activities results in inability to remove CHYLOMICRONS and TRIGLYCERIDES from the blood which has a creamy top layer after standing.Pelizaeus-Merzbacher Disease: A rare, slowly progressive disorder of myelin formation. Subtypes are referred to as classic, congenital, transitional, and adult forms of this disease. The classic form is X-chromosome linked, has its onset in infancy and is associated with a mutation of the proteolipid protein gene. Clinical manifestations include TREMOR, spasmus nutans, roving eye movements, ATAXIA, spasticity, and NYSTAGMUS, CONGENITAL. Death occurs by the third decade of life. The congenital form has similar characteristics but presents early in infancy and features rapid disease progression. Transitional and adult subtypes have a later onset and less severe symptomatology. Pathologic features include patchy areas of demyelination with preservation of perivascular islands (trigoid appearance). (From Menkes, Textbook of Child Neurology, 5th ed, p190)Colorectal Neoplasms, Hereditary Nonpolyposis: A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Skin Abnormalities: Congenital structural abnormalities of the skin.Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.46, XY Disorders of Sex Development: Congenital conditions in individuals with a male karyotype, in which the development of the gonadal or anatomical sex is atypical.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Eye Diseases, Hereditary: Transmission of gene defects or chromosomal aberrations/abnormalities which are expressed in extreme variation in the structure or function of the eye. These may be evident at birth, but may be manifested later with progression of the disorder.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Retinoschisis: A vitreoretinal dystrophy characterized by splitting of the neuroretinal layers. It occurs in two forms: degenerative retinoschisis and X chromosome-linked juvenile retinoschisis.Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.Tooth Abnormalities: Congenital absence of or defects in structures of the teeth.Anophthalmos: Congenital absence of the eye or eyes.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Pain Insensitivity, Congenital: A syndrome characterized by indifference to PAIN despite the ability to distinguish noxious from non-noxious stimuli. Absent corneal reflexes and INTELLECTUAL DISABILITY may be associated. Familial forms with autosomal recessive and autosomal dominant patterns of inheritance have been described. (Adams et al., Principles of Neurology, 6th ed, p1343)Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.NAV1.1 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that is predominantly expressed in the CENTRAL NERVOUS SYSTEM. Defects in the SCN1A gene which codes for the alpha subunit of this sodium channel are associated with DRAVET SYNDROME, generalized epilepsy with febrile seizures plus, type 2 (GEFS+2), and familial hemiplegic migraine type 3.Skin Diseases, Genetic: Diseases of the skin with a genetic component, usually the result of various inborn errors of metabolism.Spastic Paraplegia, Hereditary: A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8)Dysostoses: Defective bone formation involving individual bones, singly or in combination.Blotting, Western: 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.Tumor Suppressor Protein p53: 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.Spermine Synthase: An enzyme that catalyzes the transfer of the propylamine moiety from 5'-deoxy-5'-S-(3-methylthiopropylamine)sulfonium adenosine to spermidine in the biosynthesis of spermine. It has an acidic isoelectric point at pH 5.0. EC 2.5.1.22.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.DNA, Neoplasm: DNA present in neoplastic tissue.Genes, X-Linked: Genes that are located on the X CHROMOSOME.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Corneal Dystrophies, Hereditary: Bilateral hereditary disorders of the cornea, usually autosomal dominant, which may be present at birth but more frequently develop during adolescence and progress slowly throughout life. Central macular dystrophy is transmitted as an autosomal recessive defect.Genes, Tumor Suppressor: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Charcot-Marie-Tooth Disease: A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)Hearing Loss: A general term for the complete or partial loss of the ability to hear from one or both ears.Craniosynostoses: Premature closure of one or more CRANIAL SUTURES. It often results in plagiocephaly. Craniosynostoses that involve multiple sutures are sometimes associated with congenital syndromes such as ACROCEPHALOSYNDACTYLIA; and CRANIOFACIAL DYSOSTOSIS.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Chromosomes, Human, X: The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Infant, Newborn: An infant during the first month after birth.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Retinal Dystrophies: A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.gamma-Crystallins: A subclass of crystallins that found in the lens (LENS, CRYSTALLINE) of VERTEBRATES. Gamma-crystallins are similar in structure to BETA-CRYSTALLINS in that they both form into a Greek key-like structure. They are composed of monomeric subunits.alpha-Galactosidase: An enzyme that catalyzes the hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-galactosides including galactose oligosaccharides, galactomannans, and galactolipids.Lamin Type A: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.Cutis Laxa: A group of connective tissue diseases in which skin hangs in loose pendulous folds. It is believed to be associated with decreased elastic tissue formation as well as an abnormality in elastin formation. Cutis laxa is usually a genetic disease, but acquired cases have been reported. (From Dorland, 27th ed)Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Muscular Diseases: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesArginine: An essential amino acid that is physiologically active in the L-form.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Codon, Terminator: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.Wolfram Syndrome: A hereditary condition characterized by multiple symptoms including those of DIABETES INSIPIDUS; DIABETES MELLITUS; OPTIC ATROPHY; and DEAFNESS. This syndrome is also known as DIDMOAD (first letter of each word) and is usually associated with VASOPRESSIN deficiency. It is caused by mutations in gene WFS1 encoding wolframin, a 100-kDa transmembrane protein.Factor V Deficiency: A deficiency of blood coagulation factor V (known as proaccelerin or accelerator globulin or labile factor) leading to a rare hemorrhagic tendency known as Owren's disease or parahemophilia. It varies greatly in severity. Factor V deficiency is an autosomal recessive trait. (Dorland, 27th ed)JapanNerve Tissue ProteinsStructure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."Hypohidrosis: Abnormally diminished or absent perspiration. Both generalized and segmented (reduced or absent sweating in circumscribed locations) forms of the disease are usually associated with other underlying conditions.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.Walker-Warburg Syndrome: Rare autosomal recessive lissencephaly type 2 associated with congenital MUSCULAR DYSTROPHY and eye anomalies (e.g., RETINAL DETACHMENT; CATARACT; MICROPHTHALMOS). It is often associated with additional brain malformations such as HYDROCEPHALY and cerebellar hypoplasia and is the most severe form of the group of related syndromes (alpha-dystroglycanopathies) with common congenital abnormalities in the brain, eye and muscle development.Gonadoblastoma: A complex neoplasm composed of a mixture of gonadal elements, such as large primordial GERM CELLS, immature SERTOLI CELLS or GRANULOSA CELLS of the sex cord, and gonadal stromal cells. Gonadoblastomas are most often associated with gonadal dysgenesis, 46, XY.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.
Missense (c.785C>T; p. L262R) and nonsense (c.903G>A, p.W301X) mutations in human GIPC3 cause congenital sensorineural hearing ... In the mouse, a missense mutation in Gipc3 (c.343G>A) leads to a non-synonymous amino acid replacement (p.G115R) in the loop ... In humans, individuals with the p.W301X missense mutation (DFNB95) exhibit bilateral sensorineural hearing loss with threshold ...
ENU introduces missense point mutations; screening for mutations in a particular exon of DISC1 can produce mouse models with ...
The POLD1 missense mutation p. S478N, in the exonuclease domain, has been validated as damaging and pathogenic. Other POLD1 ...
Missense mutations in SNCA are rare. On the other hand, multiplications of the SNCA locus account for around 2% of familial ... Missense mutations of the gene (in which a single nucleotide is changed), and duplications and triplications of the locus ...
"Functional consequences of PRODH missense mutations". American Journal of Human Genetics. 76 (3): 409-20. doi:10.1086/428142. ...
Donnelly P, Menet H, Fouanon C, Herbert O, Moisan JP, Le Roux MG, Pascal O (1994). "Missense mutation in the choroideremia gene ...
Very rarely, missense mutations are observed. Mutations are often passed from one generation to the next in an autosomal ... The 508th amino acid, normally lysine, is affected by a missense mutation in some people with Birt-Hogg-Dubé syndrome. The ... In German Shepherd dogs, missense mutations in the canine ortholog of FLCN cause a similar phenotype to human BHD-kidney ...
No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a ...
All documented mutations are missense substitutions. One of the affected families has created a public website in order to ...
Zhang Z, Miteva MA, Wang L, Alexov E (2012). "Analyzing effects of naturally occurring missense mutations". Comput Math Methods ... Codon degeneracy Neutral mutation Genealogical DNA test Missense mutation Nonsense mutation Point mutation Kimchi-Sarfaty, C.; ...
"Two frequent missense mutations in Pendred syndrome". Human Molecular Genetics. 7 (7): 1099-104. doi:10.1093/hmg/7.7.1099. PMID ... phenotypic variability in two families carrying the same PDS missense mutation". American Journal of Medical Genetics. 90 (1): ...
W16 is found in the Oldenburger and is a missense mutation on Exon18. W17 is found in a Japanese Draft horse and is a missense ... It is a missense mutation on Exon12. W10 was found in a study of 27 horses in a family of American Quarter Horses, 10 of which ... W19 is a missense mutation on Exon 8 (c.1322A.G; p.Tur41Cys). This gene is predicted to be "probably damaging" and one of the ... W20 is a missense mutation on Exon14 (c.2045G>A; p.Arg682His) originally discovered in 2007 but not recognized for having a ...
2010). "GJC2 missense mutations cause human lymphedema". Am. J. Hum. Genet. 86 (6): 943-8. doi:10.1016/j.ajhg.2010.04.010. PMC ... Heterozygous missense mutations in this same gene cause pubertal onset hereditary lymphedema. GRCh38: Ensembl release 89: ...
About 80% of the mutations are missense mutations. The number and diversity of mutations results in highly variable phenotypic ... "Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations". Bone ...
Yue Q, Jen J, Nelson S, Baloh R (1997). "Progressive ataxia due to a missense mutation in a calcium-channel gene". Am J Hum ... Knight M, Storey E, McKinlay Gardner R, Hand P, Forrest S (2000). "Identification of a novel missense mutation L329I in the ... Denier C, Ducros A, Durr A, Eymard B, Chassande B, Tournier-Lasserve E (2001). "Missense CACNA1A mutation causing episodic ... "Detection of a novel missense mutation and second recurrent mutation in the CACNA1A gene in individuals with EA-2 and FHM". Hum ...
Missense mutations code for a different amino acid. A missense mutation changes a codon so that a different protein is created ... RIP creates multiple missense and nonsense mutations in the coding sequence. This hypermutation of G-C to A-T in repetitive ... For example, sickle-cell disease is caused by a single point mutation (a missense mutation) in the beta-hemoglobin gene that ... These are both examples of a non-conservative (missense) mutation. Silent mutations code for the same amino acid (a "synonymous ...
Patients with missense mutations have a better prognosis. In cases with mutations in the splice-acceptor-region, there is no ...
"Dominant missense mutations in ABCC9 cause Cantú syndrome". Nature Genetics. 44: 793-796. doi:10.1038/ng.2324. PMID 22610116. " ...
Three patients showed heterozygous de-novo missense mutation. Six patients were found with de-novo missense mutation and one ...
Bengtson P, Larson C, Lundblad A, Larson G, Påhlsson P (August 2001). "Identification of a missense mutation (G329A;Arg(110 ...
1996). "PAX6 missense mutation in isolated foveal hypoplasia". Nat. Genet. 13 (2): 141-2. doi:10.1038/ng0696-141. PMID 8640214 ... "Gene Regulation by PAX6: Structural-functional Correlations of Missense Mutants and Transcriptional Control of Trpm3/miR-204." ...
2006). "Muscle cell and motor protein function in patients with a IIa myosin missense mutation (Glu-706 to Lys)". Neuromuscul. ... 2001). "Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene". Proc. Natl. Acad ...
... a heterzyogus missense (c.1718G>T: Arg554Leu) mutation. Other missense mutations causing this disorder are unnamed; they ... Two particular missense mutations represent the majority (74% in one study of 101 individuals) of all mutations associated with ... Congenital dysfibrinogenemia is most often caused by a single autosomal dominant missense mutation in the Aα, Bβ, or γ gene; ... Unless noted as a deletion (del), frame shift (fs), or homozygous mutation, all mutations are heterozygous, missense mutations ...
Loss-of-function mutations, nonsense mutations, and missense mutations are three of the most common. Nonsense and missense ...
A missense mutation on the NET gene (SLC6A2) was discovered in which an alanine residue was replaced with a proline residue ( ... This notation for missense mutations, take Val69Ile for example, indicates that amino acid Val69 was changed to Ile. An ... Thirteen NET missense mutations have been discovered so far. Abbreviations: TMD, transmembrane domain; n/a, non-applicable. For ... However, 40 other OI patients did not have the same missense mutation, indicating other factors contributed to the phenotype in ...
A missense mutation in the mouse Col2a1 gene has been discovered, resulting in a mouse phenotype with similarities to human ... A missense mutation in the mouse Col2a1 gene causes spondyloepiphyseal dysplasia congenita, hearing loss, and retinoschisis. ...
A missense mutation occurs when a gene is altered in a way that results in a different amino acid being substituted for the one ... A missense mutation occurs when a gene is altered in a way that results in a different amino acid being substituted for the one ... A missense mutation in the gene coding for the protein hemoglobin substitutes the base thymine for adenine. This results in the ...
MISSENSE MEANDERINGS IN SEQUENCE SPACE: A BIOPHYSICAL VIEW OF PROTEIN EVOLUTION Mark A. DePristo, Daniel M. Weinreich and ... Missense Meanderings. Posted on September 29, 2005. Author William Dembski Comments(118) ... Many individual missense mutations perturb these traits by amounts that are on the same order as the permissible range of ... MISSENSE MEANDERINGS IN. SEQUENCE SPACE: A BIOPHYSICAL. VIEW OF PROTEIN EVOLUTION. Mark A. DePristo, Daniel M. Weinreich and ...
Characterization of human frataxin missense variants in cancer tissues.. Petrosino M1,2,3, Pasquo A4, Novak L1, Toto A1,5,6, ... In this study, we selected, from COSMIC database, the somatic human frataxin missense variants found in cancer tissues p.D104G ... cancer tissues; human frataxin; missense variants; protein folding; protein stability; protein variants; single amino acid ... as well as the molecular dynamics of the frataxin missense variants found in cancer tissues point to local changes confined to ...
Here we analyzed the efficacy of these inferences in 33 de novo missense mutations … ... Each persons genome sequence has thousands of missense variants. Practical interpretation of their functional significance ... Comparison of predicted and actual consequences of missense mutations Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98. ... Half of all possible missense mutations in the same 23 immune genes were predicted to be deleterious, and most of these appear ...
Missense mRNA molecules are created when template DNA strands or the mRNA strands themselves undergo a missense mutation in ... Missense mRNA molecules have one or more mutated codons that yield polypeptides with an amino acid sequence different from the ...
In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a ... Missense mutation or substitution refers to a change in one amino acid in a protein, arising from a point mutation in a single ... Not all missense mutations lead to appreciable protein changes. An amino acid may be replaced by an amino acid of very similar ... Missense mutation is a type of nonsynonymous substitution in a DNA sequence. Another type of nonsynonymous substitution is a ...
A Summary of Missense Prediction Methods. Dr. Andrew C.R. Martin, UCL. www.bioinf.org.uk. Methods and Approaches. Most ... 2007) Interpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and ... 32] Stone, E.A., and Sidow, A. (2005). Physicochemical constraint violation by missense substitutions mediates impairment of ... 2007a) CanPredict: a computational tool for predicting cancer-associated missense mutations. Nucleic Acids Res., 35, W595-W598 ...
Novel synonymous and missense variants in FGFR1 causing Hartsfield syndrome.. Courage C1,2, Jackson CB3, Owczarek-Lipska M4, ... The third case was a sporadic patient with a novel de novo heterozygous missense variant c.1868A,G, p.(Asp623Gly). ...
The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L ... The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L ... Seven missense BRCA1 C-terminal variants (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V), identified through ... Figure 2. Results of functional assay of the studied missense variants.. Percentage of transcriptional activity was expressed ...
2013a) A Y328C missense mutation in spermine synthase causes a mild form of Snyder-Robinson syndrome. Human Molecular Genetics ... 2013) Cancer missense mutations alter binding properties of proteins and their interaction networks. PloS One 8(6): e66273. ... 2012) Molecular effect of a novel missense mutation, L266V, on function of ClC‐5 protein in a Japanese patient with Dents ... Castellana S and Mazza T (2013) Congruency in the prediction of pathogenic missense mutations: state‐of‐the‐art web‐based tools ...
Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae. Alison E Gammie, Naz ... Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae Message Subject (Your Name ...
Birben E, Öner C, Öner R, Altay Ç, Gürgey A. Identification of an inframe deletion and a missense mutation in the factor XIIIA ... The first alteration, a missense mutation Leu235Arg in exon 6 of FXIIIA gene, is located in the putative calcium-binding part ... Identification of an inframe deletion and a missense mutation in the factor XIIIA gene in two Turkish patients ...
Gout is caused by deposition of monosodium urate crystals in joints when plasma uric acid levels are chronically elevated beyond the saturation threshold, mostly due to renal underexcretion of uric acid. Although molecular pathways of this underexcretion have been elucidated, its etiology remains mostly unknown. We demonstrate that gout can be caused by a mutation in LDHD within the putative catalytic site of the encoded d-lactate dehydrogenase, resulting in augmented blood levels of d-lactate, a stereoisomer of l-lactate, which is normally present in human blood in miniscule amounts. Consequent excessive renal secretion of d-lactate in exchange for uric acid reabsorption culminated in hyperuricemia and gout. We showed that LDHD expression is enriched in tissues with a high metabolic rate and abundant mitochondria and that d-lactate dehydrogenase resides in the mitochondria of cells overexpressing the human LDHD gene. Notably, the p.R370W mutation had no effect on protein localization. In line ...
... Hina Iqbal,1 Tayyba Sarfaraz,2 Farida ... Hina Iqbal, Tayyba Sarfaraz, Farida Anjum, Zubair Anwar, and Asif Mir, "Identification of Missense Mutation (I12T) in the BSND ...
Mice with missense and nonsense NF1 mutations display divergent phenotypes compared with human neurofibromatosis type I Kairong ...
A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype Message Subject (Your Name) has ... A Missense Cystic Fibrosis Transmembrane Conductance Regulator Mutation With Variable Phenotype. Eitan Kerem, Malka Nissim- ...
Author Summary The purpose of this study was to uncover the molecular basis for the champagne hair color dilution phenotype in horses. Here, we report a DNA base substitution in the second exon of the horse gene SLC36A1 that changes an amino acid in the transmembrane domain of the protein from threonine to arginine. The phenotypic effect of this base change is a diminution of hair and skin color intensity for both red and black pigment in horses, and the resulting dilution has become known as champagne. This is the first genetic variant reported for SLC36A1 and the first evidence for its effect on eye, skin, and hair pigmentation. So far, no other phenotypic effects have been attributed to this gene. This discovery of the base substitution provides a molecular test for horse breeders to test their animals for the Champagne gene (CH).
The EC5 missense allele of E-cadherin exacerbates the homozygous phenotype of the EC1 missense allele of N-cadherin. (A-F) ... Like each of the two missense mutations in the EC1 repeat of N-cadherin, the missense mutation in the EC5 repeat of N-cadherin ... Crossing females heterozygous for both the dtv43 EC5 missense allele of E-cadherin and the tb08 EC1 missense allele of N- ... Phenotypically, this EC5 missense mutant resembles an EC1 missense mutant with dominant gain-of-function, in accordance with ...
We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three ... Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. *Mike Hutton. 1. na1, ... Hutton, M., Lendon, C., Rizzu, P. et al. Association of missense and 5′-splice-site mutations in tau with the inherited ... We have now sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three ...
MAFA missense mutation causes familial insulinomatosis and diabetes mellitus Message Subject (Your Name) has sent you a message ... MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Donato Iacovazzo, Sarah E. Flanagan, Emily Walker ... Strikingly, the missense p.Ser64Phe MAFA mutation was associated with either of two distinct phenotypes, multiple insulin- ... The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its ...
Enhancers can be disrupted by single nonsense, missense and translationally silent point mutations, without recognition of an ... A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and other genes. *Hong-Xiang Liu1. nAff2, ... Liu, H., Cartegni, L., Zhang, M. et al. A mechanism for exon skipping caused by nonsense or missense mutations in BRCA1 and ... Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting ...
Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: R1699Q ... Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.. Lee, M.S.,Green ... Impact of BRCA1 BRCT Domain Missense Substitutions on Phosphopeptide Recognition.. Coquelle, N., Green, R., Glover, J.N.. (2011 ... Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.. Williams, R.S.,Glover, J.N.. (2003) J.Biol.Chem. 278 ...
... and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). ... Missense mutation in the mtDNA cytochrome b gene in a patient with myopathy Neurology. 1998 Nov;51(5):1444-7. doi: 10.1212/wnl. ... and complex III deficiency in skeletal muscle had a missense mutation in the cytochrome b gene of mitochondrial DNA (G15762A). ...
A novel missense mutation in the mouse growth hormone gene causes semidominant dwarfism, hyperghrelinemia, and obesity.. Meyer ... The SMA1-mouse is a novel ethyl-nitroso-urea (ENU)-induced mouse mutant that carries an a--,g missense mutation in exon 5 of ...
  • Our findings suggest that the homozygous recessive H2665L missense sequence variant impairs the normal morphology of the teeth roots via loss of cementum synthesis, and is also associated with early onset, recessive, Wagner syndrome, thus expanding both the phenotype mutation scenario and the inheritance mode of VCAN mutations. (frontiersin.org)
  • Both fine-mapping approaches revealed a common missense GCKR variant (rs1260326, Pro446Leu, 34% frequency, r2 = 0.93 with rs780094) as the strongest association signal in the region. (harvard.edu)
  • Whole exome sequencing revealed homozygosity for a novel missense variant affecting the evolutionary conserved amino acid Gln230 in the catalytic short-chain dehydrogenase/reductase (SDR) domain of WWOX in both girls. (deepdyve.com)
  • To our knowledge, our patients are the first individuals presenting the more severe end of the phenotypic spectrum of WWOX deficiency, although they were only affected by a single missense variant of WWOX. (deepdyve.com)
  • Exome sequencing efficiently and effectively identified a novel, homozygous missense variant in RRM2B , which was strongly suggested to be causative for arPEO. (biomedcentral.com)
  • Analysis of a Missense Variant of the Human N-formyl Peptide Receptor " by M. Bhattacharya, J. Wang et al. (uwo.ca)
  • A missense mutation in the giant protein titin is the only plausible disease-causing variant that segregates with disease among the 7 surviving affected individuals, with interrogation of the entire genome excluding other potential causes. (ahajournals.org)
  • One patient with severe type 5 hyperlipoproteinemia (MIM 144650), fasting chylomicronemia and relapsing pancreatitis resistant to standard therapy was found to be homozygous for a novel GPIHBP1 missense variant, namely G56R. (biomedcentral.com)
  • OBJECTIVE-A recent meta-analysis demonstrated a nominal association of the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K→Q missense single nucleotide polymorphism (SNP) at position 121 with type 2 diabetes. (harvard.edu)
  • We identified six rare missense mutations in this sample, including T197M in one male patient and two female controls, L201V in nine patients (three males and six females) and 4 controls (three females and one male), L213V in one female patient, A358T in one male patient and one female control, P376S in one female patient, and P419S in one male patient. (frontiersin.org)
  • We conclude that rare missense variations in most of these genes identified in individuals with retinal dystrophy cannot be confidently classified as disease-causing in the absence of additional information such as linkage or functional validation. (molvis.org)
  • CHASM substantially outperformed previously described missense mutation function prediction methods at discriminating known oncogenic mutations in P53 and the tyrosine kinase epidermal growth factor receptor. (aacrjournals.org)
  • The response profile is created for 6 ATP-competitive, reversible inhibitors against 9, 17, 5 and 17 GC-associated missense mutations of ErbB1, ErbB2, ErbB3 and ErbB4 kinase domains, respectively. (medworm.com)
  • Here, we report the results of an RNAi screen of 248 C. elegans protein kinase-encoding genes with human orthologs for enhancement of a weakly activating NRR-missense mutation of lin-12 in the Vulval Precursor Cells. (g3journal.org)
  • The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V) located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription activation (TA) assay. (plos.org)
  • Structural consequences of a cancer-causing BRCA1-BRCT missense mutation. (rcsb.org)
  • Although of limited scale, the results support the view that destabilization is the most common mechanism by which missense mutations cause monogenic disease. (proteopedia.org)
  • Some tumours have biallelic loss of function mutations but most have monoallelic missense mutations involving specific arginine residues at β-propellor tips involved in substrate recognition. (bmj.com)
  • The ubiquitin ligase sel-10 /Fbw7 is the prototype of a conserved negative regulator of lin-12 /Notch that was first defined by loss-of-function mutations that enhance lin-12 NRR-missense activity in C. elegans , and then demonstrated to regulate Notch activity in mammalian cells and to be a bona fide tumor suppressor in T-ALL. (g3journal.org)
  • Here we analyzed the efficacy of these inferences in 33 de novo missense mutations revealed by sequencing in first-generation progeny of N-ethyl-N-nitrosourea-treated mice, involving 23 essential immune system genes. (nih.gov)
  • Our mild SMA mice will be useful in (a) determining the effect of missense mutations in vivo and in motor neurons and (b) testing potential therapies in SMA. (rupress.org)
  • To determine if the preservation of some mutated sacsin protein resulted in the same cellular and behavioral alterations, we generated mice expressing an R272C missense mutation, a homozygote mutation found in some affected patients. (ozgene.com)
  • The potential effects of missense substitutions were modeled by SwissPdb Viewer based on the three-dimensional structure (PDB: 1dan) for the wild-type FVII: tissue factor complex. (haematologica.org)
  • The resulting transcript and protein product is: DNA: 5' - AAC AGC CTG CTT ACG GCT CTC - 3' 3' - TTG TCG GAC GAA TGC CGA GAG - 5' mRNA: 5' - AAC AGC CUG CUU ACG GCU CUC - 3' Protein: Asn Ser Leu Leu Thr Ala Leu Cancer associated missense mutations can lead to drastic destabilisation of the resulting protein. (wikipedia.org)
  • Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? (wikipedia.org)
  • We have developed a computational method, called Cancer-specific High-throughput Annotation of Somatic Mutations (CHASM), to identify and prioritize those missense mutations most likely to generate functional changes that enhance tumor cell proliferation. (aacrjournals.org)
  • Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug-resistance. (aacrjournals.org)
  • Here, we report that new Cer-RUB nanomicelles considerably enhance Cer in-vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. (aacrjournals.org)
  • Importantly, while in most cases CDH1 alterations result in the complete loss of E-cadherin associated with a well-established clinical impact, in about 20% of cases the mutations are of the missense type. (mdpi.com)
  • Experimental data on a set of missense mutations of the enzyme phenylalanine hydroxylase (PAH) associated with the monogenic disease phenylketonuria (PKU) have been compared with the expected in vivo impact on protein function, obtained using SNPs3D, an in silico analysis package. (proteopedia.org)