Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Preimplantation Diagnosis: Determination of the nature of a pathological condition or disease in the OVUM; ZYGOTE; or BLASTOCYST prior to implantation. CYTOGENETIC ANALYSIS is performed to determine the presence or absence of genetic disease.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.Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.Anxiety Disorders: Persistent and disabling ANXIETY.Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature.Diagnostic and Statistical Manual of Mental Disorders: Categorical classification of MENTAL DISORDERS based on criteria sets with defining features. It is produced by the American Psychiatric Association. (DSM-IV, page xxii)Genetics, Medical: A subdiscipline of human genetics which entails the reliable prediction of certain human disorders as a function of the lineage and/or genetic makeup of an individual or of any two parents or potential parents.Eugenics: The attempt to improve the PHENOTYPES of future generations of the human population by fostering the reproduction of those with favorable phenotypes and GENOTYPES and hampering or preventing BREEDING by those with "undesirable" phenotypes and genotypes. The concept is largely discredited. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Depressive Disorder, Major: Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.Genetic Diseases, Y-Linked: Genetic diseases that are linked to mutant ALLELES on the Y CHROMOSOME in humans (Y CHROMOSOME, HUMAN) or the Y chromosome in other species. Included here are animal models of human Y-linked diseases.Attention Deficit Disorder with Hyperactivity: A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V)Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Rare Diseases: A large group of diseases which are characterized by a low prevalence in the population. They frequently are associated with problems in diagnosis and treatment.Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.Stress Disorders, Post-Traumatic: A class of traumatic stress disorders with symptoms that last more than one month. There are various forms of post-traumatic stress disorder, depending on the time of onset and the duration of these stress symptoms. In the acute form, the duration of the symptoms is between 1 to 3 months. In the chronic form, symptoms last more than 3 months. With delayed onset, symptoms develop more than 6 months after the traumatic event.Autistic Disorder: A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V)Genetic 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.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Disease: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable.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.Metabolism, Inborn Errors: Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.Child Development Disorders, Pervasive: Severe distortions in the development of many basic psychological functions that are not normal for any stage in development. These distortions are manifested in sustained social impairment, speech abnormalities, and peculiar motor movements.Psychotic Disorders: Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)Genetic Counseling: An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.Substance-Related Disorders: Disorders related to substance abuse.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Cystic Fibrosis: An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.Cystic Fibrosis Transmembrane Conductance Regulator: A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.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.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.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.Judaism: The religion of the Jews characterized by belief in one God and in the mission of the Jews to teach the Fatherhood of God as revealed in the Hebrew Scriptures. (Webster, 3d ed)Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Conduct Disorder: A repetitive and persistent pattern of behavior in which the basic rights of others or major age-appropriate societal norms or rules are violated. These behaviors include aggressive conduct that causes or threatens physical harm to other people or animals, nonaggressive conduct that causes property loss or damage, deceitfulness or theft, and serious violations of rules. The onset is before age 18. (From DSM-IV, 1994)Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.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.Tic Disorders: Disorders characterized by recurrent TICS that may interfere with speech and other activities. Tics are sudden, rapid, nonrhythmic, stereotyped motor movements or vocalizations which may be exacerbated by stress and are generally attenuated during absorbing activities. Tic disorders are distinguished from conditions which feature other types of abnormal movements that may accompany another another condition. (From DSM-IV, 1994)Syndrome: A characteristic symptom complex.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Psychiatric Status Rating Scales: Standardized procedures utilizing rating scales or interview schedules carried out by health personnel for evaluating the degree of mental illness.Chromosome Disorders: 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)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.Borderline Personality Disorder: A personality disorder marked by a pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts. (DSM-IV)Somatoform Disorders: Disorders having the presence of physical symptoms that suggest a general medical condition but that are not fully explained by a another medical condition, by the direct effects of a substance, or by another mental disorder. The symptoms must cause clinically significant distress or impairment in social, occupational, or other areas of functioning. In contrast to FACTITIOUS DISORDERS and MALINGERING, the physical symptoms are not under voluntary control. (APA, DSM-V)Molecular Biology: A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Human Genome Project: A coordinated effort of researchers to map (CHROMOSOME MAPPING) and sequence (SEQUENCE ANALYSIS, DNA) the human GENOME.Cognition Disorders: Disturbances in mental processes related to learning, thinking, reasoning, and judgment.Sphingolipidoses: A group of inherited metabolic disorders characterized by the intralysosomal accumulation of SPHINGOLIPIDS primarily in the CENTRAL NERVOUS SYSTEM and to a variable degree in the visceral organs. They are classified by the enzyme defect in the degradation pathway and the substrate accumulation (or storage). Clinical features vary in subtypes but neurodegeneration is a common sign.Sleep Disorders: Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)Lipid Metabolism Disorders: Pathological conditions resulting from abnormal anabolism or catabolism of lipids in the body.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.Probability Theory: The branch of mathematics dealing with the purely logical properties of probability. Its theorems underlie most statistical methods. (Last, A Dictionary of Epidemiology, 2d ed)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).Nonsense Mediated mRNA Decay: An mRNA metabolic process that distinguishes a normal STOP CODON from a premature stop codon (NONSENSE CODON) and facilitates rapid degradation of aberrant mRNAs containing premature stop codons.Targeted Gene Repair: A technique which uses synthetic oligonucleotides to direct the cell's inherent DNA repair system to correct a mutation at a specific site in an episome or chromosome.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.Fanconi Anemia: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)Heterozygote: An individual having different alleles at one or more loci regarding a specific character.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)Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Heterozygote Detection: Identification of genetic carriers for a given trait.Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified.Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics.Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Mitochondrial Diseases: Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.Tuberous Sclerosis: Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.Alcohol-Related Disorders: Disorders related to or resulting from abuse or mis-use of alcohol.Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.Movement Disorders: Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.Tay-Sachs Disease: An autosomal recessive neurodegenerative disorder characterized by the onset in infancy of an exaggerated startle response, followed by paralysis, dementia, and blindness. It is caused by mutation in the alpha subunit of the HEXOSAMINIDASE A resulting in lipid-laden ganglion cells. It is also known as the B variant (with increased HEXOSAMINIDASE B but absence of hexosaminidase A) and is strongly associated with Ashkenazic Jewish ancestry.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.Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language.Combat Disorders: Neurotic reactions to unusual, severe, or overwhelming military stress.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Genetic Variation: Genotypic differences observed among individuals in a population.Muscular Dystrophy, Duchenne: An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)Attention Deficit and Disruptive Behavior Disorders: Includes two similar disorders: oppositional defiant disorder and CONDUCT DISORDERS. Symptoms occurring in children with these disorders include: defiance of authority figures, angry outbursts, and other antisocial behaviors.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.Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification or release of tension at the time of committing the act.Homozygote: An individual in which both alleles at a given locus are identical.Consanguinity: The magnitude of INBREEDING in humans.Hemochromatosis: A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.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)Models, Biological: 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.Dysautonomia, Familial: An autosomal disorder of the peripheral and autonomic nervous systems limited to individuals of Ashkenazic Jewish descent. Clinical manifestations are present at birth and include diminished lacrimation, defective thermoregulation, orthostatic hypotension (HYPOTENSION, ORTHOSTATIC), fixed pupils, excessive SWEATING, loss of pain and temperature sensation, and absent reflexes. Pathologic features include reduced numbers of small diameter peripheral nerve fibers and autonomic ganglion neurons. (From Adams et al., Principles of Neurology, 6th ed, p1348; Nat Genet 1993;4(2):160-4)Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Cell Line: Established cell cultures that have the potential to propagate indefinitely.beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.Schizophrenia: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.Factor IX: Storage-stable blood coagulation factor acting in the intrinsic pathway. Its activated form, IXa, forms a complex with factor VIII and calcium on platelet factor 3 to activate factor X to Xa. Deficiency of factor IX results in HEMOPHILIA B (Christmas Disease).Hemophilia B: A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008)Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Chromosomes, Human: Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.Antisocial Personality Disorder: A personality disorder whose essential feature is a pervasive pattern of disregard for, and violation of, the rights of others that begins in childhood or early adolescence and continues into adulthood. The individual must be at least age 18 and must have a history of some symptoms of CONDUCT DISORDER before age 15. (From DSM-IV, 1994)
  • Over the last 20 years, following-up on the study of Mendelian susceptibility to mycobacterial disease (MSMD), monogenic disorders have been found to underlie TB in some patients. (springer.com)
  • By contrast, the genetic risk for SCD in older adults is more complex, with few if any unifying hypotheses about molecular mechanisms, although some overlap is observed with susceptibility to monogenic arrhythmia. (jci.org)
  • Advances in genetics have increased the ease and decreased the cost of identifying genetic differences that contribute to disease susceptibility. (jci.org)
  • This article presents the general pediatrician with a broad overview of the rapidly expanding spectrum of primary immune deficiencies, which are diseases that go beyond the classic description of increased susceptibility to infections and also those with predisposition to autoimmunity, malignancy, and immune dysregulation. (healio.com)
  • Autosomal dominant (AD) GATA2 deficiency is the only one of these IEIs leading to a pleiotropic syndromic disorder that manifests as a lack of multilymphoid and granulocyteCmacrophage progenitors in the bone marrow, smaller amounts of dendritic cells (DCs), monocytes, T, NK and B lymphocytes in peripheral bloodstream, and higher susceptibility to viral, mycobacterial, and fungal attacks. (clarkfrancis.com)
  • Recently, the role of genetic factors of the host has been extensively studied, revealing their influence on the susceptibility to or the severity of sepsis. (biomedcentral.com)
  • Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-resp. (biomedcentral.com)
  • The identification and avoidance of disease susceptibility in embryos is the most common goal of preimplantation genetic diagnosis (PGD). (unboundmedicine.com)
  • A1 - Krahn,Timothy, Y1 - 2008/11/01/ PY - 2007/12/21/received PY - 2008/10/03/accepted PY - 2008/11/4/pubmed PY - 2009/7/16/medline PY - 2008/11/4/entrez SP - 187 EP - 202 JF - Medicine, health care, and philosophy JO - Med Health Care Philos VL - 12 IS - 2 N2 - The identification and avoidance of disease susceptibility in embryos is the most common goal of preimplantation genetic diagnosis (PGD). (unboundmedicine.com)
  • susceptibility to a wide range of diseases (e.g. sickle-cell anemia, β- thalassemia and cystic fibrosis result from SNPs). (edwardbetts.com)
  • The pathogenesis of tuberculosis (TB) remains poorly understood, as no more than 5-10% of individuals infected with Mycobacterium tuberculosis go on developing clinical disease. (springer.com)
  • We also describe the clinical features of liver disease in some monogenic forms of PID included in the clinical spectrum of CVID as ICOS, NFKB1, NFKB2, CTLA-4, PI3Kδ pathway, ADA2, and IL21-R genetic defects. (frontiersin.org)
  • However, monogenic forms only account for 2-10% CVID clinical diagnosis ( 6 ). (frontiersin.org)
  • Mirroring this immunologic and genetic heterogeneity, CVID patients may experience a wide spectrum of clinical manifestations during the course of their life, including recurrent bacterial infections (mainly of gastrointestinal and respiratory tracts) and various disorders related to immune dysregulation, such as autoimmunity, granulomata, lymphoid hyperplasia, enteropathy and malignancies ( 15 - 17 ). (frontiersin.org)
  • A human genetic theory of infectious diseases has emerged gradually from clinical and epidemiological studies, building on many elegant studies in plants and animals. (pnas.org)
  • For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. (pnas.org)
  • A century later, although we are able to prevent many human infectious diseases through hygiene and vaccination and to cure others by drug treatment or surgery, we still do not fully understand the root causes of most infectious diseases and their clinical variability. (pnas.org)
  • The Journal of Biochemical and Clinical Genetics (JBCGenetics) aims to provide continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as phenotype analysis within the current context of genotype/phenotype correlations. (jbcgenetics.com)
  • Clinical presentation of SLE is extremely heterogeneous and different groups of disease are likely to exist. (meta.org)
  • Heredity represents the single largest etiology of the epilepsies, a common and extremely heterogeneous set of neurologic disorders defined by repeated clinical seizure episodes linked to aberrant electrical synchronization of the brain. (mhmedical.com)
  • Many represent a heterogeneous collection of disorders with imprecise classification criteria and overlapping clinical presentations. (jci.org)
  • Clinical WES therefore requires thorough genetic counseling to prepare subjects for unexpected findings and to explain results. (biomedcentral.com)
  • This short turnaround time was achieved by technical improvements in sample preparation and sequencing in combination with development of an automated correlation tool for prioritization of clinical information to assist interpretation, and focused on analysis of 591 monogenic diseases with early pediatric presentation. (biomedcentral.com)
  • By analyzing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization, we show that clinical diagnosis of genetic disorders can be obtained within 15-36 hours. (biomedcentral.com)
  • Learning is easy with the aid of clear, full-color illustrative diagrams, a wealth of clinical photographs of genetic diseases, multiple-choice and case-based review questions, end-of-chapter summaries, and convenient online access at www.studentconsult.com. (elsevier.com)
  • Visualize the appearance of genetic disorders with a fantastic art program that presents many clinical photos of genetic diseases, and work through complicated ideas with an array of full-color illustrative diagrams. (elsevier.com)
  • To describe the demographic details of patients with IDCM who presented at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), and to determine if there is evidence of familial disease through family history assessment and clinical screening of relatives. (scielo.org.za)
  • Most of these disorders display incomplete clinical penetrance, with the possible exception of DBR1 deficiency. (springer.com)
  • These findings pave the way for the gradual definition of the genetic and immunological architecture of childhood HSE, with both biological and clinical implications. (springer.com)
  • My professional goal as a pediatrician specializing in immunology, has been to challenge the limits of 'inexplicable' and 'untreatable' diseases, and apply current scientific knowledge to understand the mechanisms of impaired cellular immune function underlying the clinical manifestations in order to develop curative treatments. (stanford.edu)
  • I plan to implement robust functional studies to define the consequences of these genetic abnormalities and bridge them to the patient's clinical phenotype. (stanford.edu)
  • CMJAH), and to determine if there is evidence of familial disease through family history assessment and clinical screening of relatives. (who.int)
  • The clinical consequences of excessive oxalate excretion are nephrolithiasis and/or nephrocalcinosis, and/or the early-onset end-stage renal disease (ESRD) in childhood. (biomedcentral.com)
  • Revealing monogenic holes in the host defense of otherwise healthy humans also has profound clinical implications, offering many families worldwide the possibility of molecular diagnosis and genetic counseling, as well as treatments aimed at restoring a deficient immune response. (rockefeller.edu)
  • Patients experience neuropathic pain, kidney failure, heart disease, and strokes.Scope of reviewThe clinical picture and molecular features of Fabry disease are described, along with updates on disease mechanisms, animal models, and therapies.Major conclusionsHow the accumulation of α-ga. (medworm.com)
  • As clinical management of inherited metabolic diseases (IMDs) has improved, more patients affected by these conditions are surviving into adulthood. (oup.com)
  • Inherited Metabolic Disease in Adults offers an authoritative clinical guide to the adult manifestations of these challenging and myriad conditions. (oup.com)
  • In addition to her clinical and research efforts, Dr. Vanderver leads the Global Leukodystrophy Initiative , an advocacy group that includes parents, clinicians and researchers, to raise disease awareness and ensure that patients receive appropriate social and medical support. (chop.edu)
  • 19. Postorino V, Sanges V, Giovagnoli G, Fatta LM, De Peppo L, Armando M, Vicari S, Mazzone L. Clinical differences in children with autism spectrum disorder with and without food selectivity . (cra-rhone-alpes.org)
  • For rare genetic disorders (e.g., mitochondrial diseases), innovative "N-of-1" precision trials tailored to each individual patient could address the limitations of clinical research in rare disease populations. (nap.edu)
  • John Staropoli, associate medical director at Biogen, discussed genetic testing and clinical drug development for spinal muscular atrophy (SMA). (nap.edu)
  • The current review provides an update focused on the evolving epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease expression, advances in clinical assessment of withdrawal, novel approaches to NAS treatment, and the emerging role of quality improvement in assessment and management of NAS. (readbyqxmd.com)
  • Clinical phenotypes are heterogenous and resemble Behçet's disease, juvenile idiopathic arthritis, inflammatory bowel disease, or periodic fever syndrome, with symptoms developing at an early age. (bvsalud.org)
  • This unfortunate incident resulted in a moratorium on clinical trials here in the U.S. for years, until companies came back with what I see as safer technologies, and technologies focused on life-threatening diseases. (biomedreports.com)
  • For example, there is a large initiative in the USA called "Clinical and Basic Investigations into Known and Suspected Congenital Disorders of Glycosylation" and also the RareCommons Spanish project. (apcdg.com)
  • The puzzle of symptomatic febrile attacks recurring over time in children requires evaluating the mixture of clinical data, inflammatory parameters in different disease phases, the therapeutic efficacy of specific drugs such as colchicine, corticosteroids or IL-1 antagonists, and genotype analysis in selected cases. (mjhid.org)
  • abstract = "Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. (hud.ac.uk)
  • The aim of this study was to estimate the burden of monogenic disease-causing variants in Indian populations. (cdc.gov)
  • Toward this, we have assessed the frequency profile of monogenic phenotype-associated ClinVar variants. (cdc.gov)
  • Herein, we discuss genetic variants subdivided into those that shorten telomeres, activate the DNA damage response, change resident protein expression or function, or affect organelle activity. (jci.org)
  • In addition, these studies reveal interactions between genetic variants, environmental factors, and age that influence the phenotypic spectrum of disease. (jci.org)
  • High-throughput, "next-generation" technologies make it possible to sequence entire human genomes, allowing for the identification of many new genetic variants that contribute to organ fibrosis. (jci.org)
  • Genetic variants are subclassified by their frequency in the general population. (jci.org)
  • Most common variants linked to fibrotic diseases by genome-wide association studies (GWAS) are located in noncoding regions of the genome. (jci.org)
  • Genetic variants that occur at lower frequencies are termed "rare. (jci.org)
  • Although rare variants are individually uncommon, they represent the larger class of genetic variants. (jci.org)
  • PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis. (nih.gov)
  • Most metabolic disorders represent a spectrum of phenotypes from normal via attenuated to severe (and sometimes prenatally fatal), and disease manifestation is often influenced by other specific genetic or exogenous factors. (springer.com)
  • Systemic lupus erythematosus (SLE) is a severe lifelong multisystem autoimmune disease characterized by the presence of autoantibodies targeting nuclear autoantigens, increased production of type I interferon and B cell abnormalities. (meta.org)
  • This category includes disorders that are considered the classic PIDs, which predispose patients to severe, recurrent, and unusual infections. (healio.com)
  • Staphylococcus aureus has emerged as a leading cause of invasive severe diseases with a high rate of morbidity and mortality worldwide. (biomedcentral.com)
  • A combination of virulence and host factors might explain this unique severe form of staphylococcal disease. (biomedcentral.com)
  • Humans are a natural reservoir of S. aureus , which can occasionally cause diseases that range in severity from minor skin infections to severe cases of pneumonia, bacteremia and septic shock [ 1 ]. (biomedcentral.com)
  • Thromboembolic disease is a complex disorder with a multifactorial aetiology and a severe outcome. (readbyqxmd.com)
  • However, in severe cases of inherited disease, inflammation can be chronic with persistent symptoms and development of long-term complications. (psychiatryadvisor.com)
  • A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). (biomedcentral.com)
  • Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder associated with high mortality. (sciencemag.org)
  • Publication date: Available online 14 September 2019Source: Biochimica et Biophysica Acta (BBA) - General SubjectsAuthor(s): James J. Miller, Adam J. Kanack, Nancy M. DahmsAbstractBackgroundFabry disease is caused by α-galactosidase A deficiency. (medworm.com)
  • Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. (bvsalud.org)
  • MPS II is a genetic lysosomal storage disease caused by deficiency of the iduronate-2-sulfatase (IDS) enzyme which is needed to break down or recycle glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate. (sangamo.com)
  • He had a mild form of a disease caused by an enzyme deficiency. (biomedreports.com)
  • Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait's penetrance and expressivity. (genetics.org)
  • This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue. (pnas.org)
  • Epilepsy is a chronic brain disease that is characterized by an enduring predisposition to recurrent unprovoked epileptic seizures. (geneticseducation.ca)
  • We were able to classify malformations in one of the four groups using the three most important methods of human genetic investigations: (a) chromosomal analysis, (b) family investigations, (c) twin method. (semanticscholar.org)
  • The proportion increases to 30% when considering CVID cases with criteria of monogenic form suspicion including early onset, autoimmune/inflammatory manifestations, low B lymphocytes, and/or familial history of hypogammaglobulinemia ( 7 ). (frontiersin.org)
  • To investigate novel genetic defects to lead to very early onset intestinal inflammation we established the COLORS in IBD study ( COL itis of early O nset - R are disease S with IN IBD ). (ox.ac.uk)
  • Having moved off the threshold of permitting PGD testing for only fatal (or seriously debilitating), early-onset diseases, I will investigate reasons for why age of onset will not do any work to discriminate between which adult-onset diseases should be considered serious or not. (unboundmedicine.com)
  • Her work includes genetic diagnostics by use of exome sequencing (including analysis, interpretation of results and reporting) in primary immune deficiencies, hematological malignancies and other rare disorders. (fimm.fi)
  • In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease . (springer.com)
  • Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. (nih.gov)
  • The mission of the Institute is to advance new fundamental understanding of the molecular, cellular and etiological basis of human diseases. (fimm.fi)
  • 5 ] solved the problem of exclusivity by adding "molecular" before encompassing every disease of the "textbook of the future. (iospress.com)
  • The study presents metabolomic and molecular-genetic findings in a patient with PH2. (biomedcentral.com)
  • Offer molecular genetic testing if a PAX2 pathogenic variant has been identified in an affected family member. (nih.gov)
  • Autoinflammatory diseases refer to disorders in which local factors lead to the activation of innate immune cells, causing tissue damage when in the absence of autoantigens and autoantibodies. (bvsalud.org)
  • in others, the seizure disorder may be stationary for prolonged periods, or herald the onset of even more frequent seizures, progressive neurologic deficits, or death. (mhmedical.com)
  • Diseases characterized by progressive fibrosis, especially those of late onset, are complex and difficult to study. (jci.org)
  • The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. (nih.gov)
  • The Warren Family Research Center for Drug Discovery and Development (Warren Center) at the University of Notre Dame is a state-of-the-art resource for a highly productive and renowned group of drug discovery faculty with expertise and interest in areas such as neurological and central nervous system disorders, infectious disease, cancer and rare diseases. (nd.edu)
  • CDG: a victim of limit budget on rare diseases? (apcdg.com)
  • You are driving basic and applied research for CDG and related rare diseases. (apcdg.com)
  • Domenica Taruscio, M.D. , is the Director of the National Centre for Rare Diseases at the Italian National Institute of Health (Istituto Superiore di Sanità) in Rome, Italy. (icord2019.org)
  • EPIRARE, EUROPLAN, European Joint Programme on Rare Diseases. (icord2019.org)
  • Aran-Duchenne disease spinal muscular atrophy . (thefreedictionary.com)
  • For example, pre-symptomatic intervention in spinal muscular atrophy yields much better outcomes than symptomatic intervention, supporting the case for newborn screening for this genetic disorder. (nap.edu)