Genetic disorder

Immunity29

• Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of monogenic inborn errors of immunity with a wide spectrum of clinical manifestations. (frontiersin.org)
• Rare inborn errors of immunity, such as autosomal recessive, complete IL-12Rβ1 and TYK2 deficiencies, impairing the IL-12- and IL-23-dependent induction of IFN-γ, were initially identified in a few patients. (springer.com)
• Both rare and common genetic etiologies of TB affect IFN-γ immunity, providing a rationale for novel preventive and therapeutic approaches for TB control, including the use of recombinant IFN-γ. (springer.com)
• The International Union of Immunological Societies (IUIS) Expert Primary Immunodeficiency Committee (now called Expert Committee on inborn errors of immunity - IEI) redefined in 2009 the acronym CVID as "common variable immunodeficiency disorders," thus highlighting the heterogeneity of the underlying immune defects ( 3 ). (frontiersin.org)
• The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. (bvsalud.org)
• Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. (bvsalud.org)
• As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. (bvsalud.org)
• Her breakthrough translational research intersects two distinct but interrelated areas: inducing immune tolerance following hematopoietic stem cell and progenitor cell transplantation (HSPCT) and designing novel gene and cell therapy approaches for patients with inborn errors of immunity and hematological malignancies. (stanford.edu)
• bubble boy disease"), a life-threatening inborn error of immunity. (stanford.edu)
• PIDs are also referred to as inborn errors of immunity to reflect the fact that they are genetic in nature and to distinguish them from secondary immune defects, such as those caused by infections (eg, HIV), severe malnutrition, chemotherapy, and severe burns. (healio.com)
• The most severe form of these disorders is severe combined immune deficiency (SCID), followed by combined immune deficiencies (CID), humoral or antibody defects, and innate immunity defects. (healio.com)
• A major focus of these studies is to understand the role of ubiquitination in regulating intestinal barrier function, immunity, and to characterize links with human inflammatory bowel disease. (phenogenomics.cz)
• Over the last 15 years, human genetic and immunological studies have provided proof-of-principle that childhood HSE can result from inborn errors of central nervous system (CNS)-specific, cell-intrinsic immunity to HSV-1. (springer.com)
• Alcais A, Quintana-Murci L, Thaler DS, Schurr E, Abel L, Casanova JL (2010) Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity? (springer.com)
• Casanova JL (2015b) Severe infectious diseases of childhood as monogenic inborn errors of immunity. (springer.com)
• 2019). Recently discovered inborn errors of immunity (IEIs) have exhibited that life-threatening influenza pneumonitis or encephalitis can be caused by monogenic defects of innate/intrinsic immunity (Bigley et al. (clarkfrancis.com)
• 2018). Here, we discuss the human genetic determinism of life-threatening influenza pneumonitis, which is usually rapidly changing our understanding of both clinical influenza and the basic principles of antiviral immunity. (clarkfrancis.com)
• Tests the hypothesis that life-threatening disease during primary infection results from inborn errors of immunity. (rockefeller.edu)
• He searches for single-gene mutations that selectively compromise the immunity of otherwise healthy children and adults who are exquisitely vulnerable to specific infectious diseases, including the novel coronavirus (SARS-CoV-2). (rockefeller.edu)
• The team has a particular interest in so-called inborn errors of immunity, the genetic variations that affect a person's ability to fight off an infectious agent. (rockefeller.edu)
• These inborn errors of immunity to infection can be rare or common, and can affect children or adults. (rockefeller.edu)
• Building on their identification of a large group of errors in IFN-γ immunity responsible for severe clinical disease caused by poorly virulent mycobacteria, Casanova and Abel discovered the first cases of rare and common monogenic forms of bona fide tuberculosis. (rockefeller.edu)
• Since the outbreak of the coronavirus pandemic, Casanova has been sequencing the genomes of previously healthy young patients with life-threatening COVID-19, searching for genetic variations that may explain their insufficient immunity to SARS-CoV-2. (rockefeller.edu)
• Rare monogenic inborn errors of immunity were found to predispose to severe infectious diseases, such as mutations that impair NF-κB responses [ 5 ]. (biomedcentral.com)
• Mouse genetic studies demonstrated that interferon (IFN)-α/β immunity defects increased susceptibility to virus-induced myocarditis. (onlinejacc.org)
• Tests the hypothesis that severe disease during primary infection can result from monogenic inborn errors of immunity. (rockefeller.edu)
• Systemic autoinflammatory disorders (SAIDs) are inherited defects of innate immunity characterized by recurrent sterile inflammatory attacks involving skin, joints, serosal membranes, gastrointestinal tube, and other tissues, which recur with variable rhythmicity and display reactive amyloidosis as a potential long-term complication. (mjhid.org)
• In addition to being crucial for pathogen recognition through the mammalian cysteine protease caspase-1, a central enzyme of innate immunity, which processes pro-interleukin-1 (IL- 1)β into the mature proinflammatory cytokine IL- 1β, the discovery of monogenic and polygenic disorders in which inflammasome activity and IL- 1 release are deregulated highlights the essential importance of inflammasome-supervised human defences against infections. (mjhid.org)
• 1 ] Different studies have demonstrated the existence of a functional hierarchy of proinflammatory cytokines in systemic autoinflammatory disorders (SAIDs), a heterogeneous cluster of rare genetically determined diseases involving innate immunity, mainly characterized by the recurrence of inflammatory flares affecting the skin, joints, serosal membranes, gastroenteric tube, central nervous system and other tissues, in which IL-1β is the most critical driver of inflammation at different levels. (mjhid.org)

Errors30

• Over the years, his laboratory has discovered the genetic causation for more than 20 diseases, including those responsible for inborn errors of metabolism, inherited retinal degeneration, disorders of cellular organelle biogenesis and genetic variations that contribute risk for common disorders such as schizophrenia. (hopkinsmedicine.org)
• In the past, our lab has focused primarily on rare monogenic disorders including inborn errors of amino acid metabolism as well as various human retinal degenerations. (hopkinsmedicine.org)
• Similarly, we are interested in inborn errors of biogenesis and function of the peroxisome, a ubiquitous sub-cellular organelle whose protein components participate in numerous metabolic pathways. (hopkinsmedicine.org)
• Inborn errors of metabolism used to be regarded as simple monogenic traits, but a closer look at how different alleles of a gene determine different phenotypes shows that the molecular mechanisms in the individual case are often complicated. (springer.com)
• Furthermore, the respective contributions of genetic and acquired factors to pathogenesis vary along the spectrum of age, with inborn errors having the greatest impact on SCD risk in younger subjects and acquired factors dominating risk in older subjects. (jci.org)
• inborn errors of metabolism (IEM), newborn screening, carrier detection, mitochondrial disorders, laboratory aspects of IEM and medications used in the treatment of IEM. (jbcgenetics.com)
• Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. (biomedcentral.com)
• Most congenital metabolic disorders known as inborn errors of metabolism result from single-gene defects. (wikipedia.org)
• Inborn errors of metabolism are generally categorized as rare diseases. (iospress.com)
• The term "inborn errors of metabolism" was first used by Sir Archibald Garrod in his Croonian Lectures in 1908 [ 1 ] and in his monograph Inborn Errors of Metabolism in 1909 [ 2 ]. (iospress.com)
• He defined these inborn errors as genetically determined diseases caused by blocks in the metabolic pathways due to deficient activity of an enzyme [ 3 ]. (iospress.com)
• Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. (biomedcentral.com)
• Inborn errors of metabolism (IEM) are rare genetic diseases, which usually have a recessive mode of inheritance. (biomedcentral.com)
• Ornithine transcarbamylase (OTC) deficiency (OTCD) is an X-linked recessive disorder that accounts for nearly half of all inborn errors of the urea cycle ( 1 ). (sciencemag.org)
• Monogenic inborn errors confer susceptibility to forebrain (TLR3-IFN or snoRNA31) or brainstem (DBR1) HSE. (springer.com)
• Friedreich's ataxia, Barth syndrome, mitochondrial myopathies and cardiomyopathy (IDCM) was the second most common form of numerous inborn errors of metabolism. (who.int)
• Screening of inborn errors of metabolism, including the performance of GC/MS urine organic acid profiling and HPLC amino acid profiling, showed abnormalities, which suggested deficiency of GRHPR enzyme. (biomedcentral.com)
• This articles provides an overview and discussion on an important area of the treatment of inborn errors of metabolism. (ommbidblog.com)
• Ramedis is a web-based information system for inborn errors of metabolism. (ommbidblog.com)
• Inborn errors of metabolism (IEMs), such as cystic fibrosis and galactosemia, are often monogenic diseases that are individually rare but common as a class (in the United States at least 1 in 5000 live births is affected by an IEM) ( Gupta 2007 ). (genetics.org)
• GSDs are monogenic recessive inborn (inherited) errors in metabolism involving improper production or breakdown of energy stored as glycogen. (nd.edu)
• Biochemical and Molecular Genetics of Human Disease I. Monogenic disorders Garrod's Inborn Errors of Metabolism G6PD deficiency Alpha-1 antitrypsin deficiency Familial hypercholesterolemia Hemophilia Heritable disorders of collagen. (slideserve.com)
• For some types of inborn errors of metabolism, the development of MR can be avoided with special diets or supplements and for others treatment can reduce the severity of the symptoms 7 . (scielosp.org)
• Therapies are becoming increasingly avaible for inborn errors of metabolism making diagnosis of these disorders particularly improtant. (ommbidblog.com)
• Posted February 25th, 2015 by Alina Levtova & filed under Exome sequencing , Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT . (ommbidblog.com)
• Posted July 22nd, 2014 by Yannis Trakadis & filed under Exome sequencing , Part 06: DIAGNOSTIC APPROACHES , Part 28: NEUROGENETICS , Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT . (ommbidblog.com)
• Inborn errors of metabolism were excluded. (biomedcentral.com)
• The data were presented today at the 2018 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) being held in Athens, Greece . (sangamo.com)
• gene: AGPS was added gene: AGPS was added to Inborn errors of metabolism. (genomicsengland.co.uk)
• These results suggest that there may be substantial genetic effects on amino acid levels in the general population that may underlie inborn errors of metabolism. (biomedcentral.com)

Genes29

• Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. (frontiersin.org)
• Five novel disease-causing genes were discovered. (frontiersin.org)
• In particular, our studies involve clinical, biochemical, molecular and therapeutic aspects of specific human genetic diseases as well as more global studies of the network interactions and consequences of the genes and proteins implicated in human disease. (hopkinsmedicine.org)
• We also have a special interest in peroxisomal ABC transporters and have produced knockout mice for the genes encoding some of these to elucidate the function of these transporters and their role in human genetic disease. (hopkinsmedicine.org)
• Mendelian (i.e., monogenic) syndromes predisposing to life-threatening ventricular arrhythmias in young adults and children are genetically heterogeneous, with more than 25 genes identified so far (Table 1 ). (jci.org)
• Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. (bvsalud.org)
• She was the original plaintiff in the Supreme Court case that overturned the ability to patent genes and served on the Institute of Medicine Committee on Genetic Testing. (columbiadoctors.org)
• We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. (biomedcentral.com)
• The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. (biomedcentral.com)
• Interrogation of all protein-coding genes results in a high diagnostic yield, but also leads to identification of genetic variants of unclear relationship with the disease under investigation as well as secondary (incidental) findings. (biomedcentral.com)
• An alternative approach focuses on subsets of monogenic disorders, enabled by filtering of exome data against a panel of selected monogenic disease genes. (biomedcentral.com)
• Currently, Dr. Roncarolo is designing a gene therapy strategy to correct mutations in IL-10 and IL-10 receptor genes, which cause devastating very early onset inflammatory bowel disease (VEO-IBD), by CRISPR-based gene correction of patient HSPCs. (stanford.edu)
• Genetic disorders may be hereditary , meaning that they are passed down from the parents' genes. (wikipedia.org)
• For example, achondroplasia is typically considered a dominant disorder, but children with two genes for achondroplasia have a severe skeletal disorder of which achondroplasics could be viewed as carriers. (wikipedia.org)
• X-linked dominant disorders are caused by mutations in genes on the X chromosome . (wikipedia.org)
• In recent years, mouse and rat models have been considered excellent models in the search for functions of genes within complex organisms as most of their physiological functions are very similar to those of humans and, also, their genetic differences are minimal (in comparison to other non-mammalian models). (phenogenomics.cz)
• These two genes are likely to be involved both in monogenic recessive and digenic/oligogenic KS transmission modes. (nature.com)
• Notably, mutations in any of the above-mentioned KS genes have been found in less than 30% of the KS patients, which indicates that other genes involved in the disease remain to be discovered. (nature.com)
• Mutations in any of the five known disease genes ( KAL1 , FGFR1 , FGF8 , PROKR2 , PROK2 ) have been identified in a relatively small proportion (less than 30%) of the patients. (nature.com)
• The Online Mendelian Inheritance in Man database currently contains ∼3000 human genes "with a phenotype-causing mutation" ( http://omim.org/ ), including many diseases caused by complete or partial loss of gene function. (genetics.org)
• Perlara is the first biotech public benefit corporation (bioPBC) that discovers cures for rare diseases and learns how genes work across diseases to map connections to common ailments. (nd.edu)
• Publication date: Available online 12 September 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Kauss Valerjans, Dambrova Maija, Medina Diego LuisAbstractNeuronal ceroid lipofuscinoses, also collectively known as Batten disease, are a group of rare monogenic disorders caused by mutations in at least 13 different genes. (medworm.com)
• ic [ dʒə netık ] adjective ** relating to genes and the study of them: Doctors believe the condition is caused by a genetic defect. (enacademic.com)
• genetic */*/ - UK [dʒəˈnetɪk] / US adjective biology relating to genes, or to the study of genes Doctors believe the condition is caused by a genetic defect. (enacademic.com)
• Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below. (genomicsengland.co.uk)
• AbstractAutosomal dominant polycystic kidney disease (ADPKD), caused by mutations inPKD1 orPKD2 genes, is the most common hereditary renal disease. (medworm.com)
• Candidate variants in known disease‐causing genes were identified for further investigation by comparison with the fetal phenotype. (omictools.com)
• Among more than 5,000 human monogenic disorders with known causative genes, transposable element insertion of a Long Interspersed Nuclear Element 1 (LINE1, L1) is known as the mechanistic basis in only 13 genetic conditions. (elsevier.com)
• In fact, clinical and molecular studies have demonstrated that several disease genes implicated in syndromes with AVCD encode proteins that participate in ciliary function. (biomedcentral.com)

Mutations21

• The term 'variable expressivity' is not helpful with regard to autosomal recessive disorders when variable phenotypes are explained by different mutations in the respective gene. (springer.com)
• Alam NA, Rowan AJ, Wortham NC, et al (2003) Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency. (springer.com)
• Chromosomal disorders (gene and chromosome mutations). (semanticscholar.org)
• 2. Single (monogenic) hereditary anomalies and malformations (gene mutations: point-mutations). (semanticscholar.org)
• Recently, childhood-onset SLE (cSLE) cases have been linked to single gene mutations, defining the concept of monogenic or Mendelian lupus. (meta.org)
• The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. (biomedcentral.com)
• In other genetic disorders, defects may be caused by new mutations or changes to the DNA . (wikipedia.org)
• or 2) disorders associated with known genetic mutations that have altered cellular physiology such as the chloride channel defect in cystic fibrosis or caused severe structural, cellular, or subcellular abnormalities. (iospress.com)
• Prenatal testing for high-risk pregnancies may be discussed if the disease-causing mutations in the family are known. (biomedcentral.com)
• Ribosomopathies are a group of rare diseases characterized by an impaired synthesis or function of ribosomes, caused by inherited genetic mutations. (academicpositions.nl)
• As many as 30% of the mutations found in FGFR1 might be de novo mutations, certainly a possibility to be considered before assessing recurrence risk of this genetic form in a family. (nature.com)
• Yeast strains with loss-of-function mutations in the yeast ortholog ( GAL7 ) of the human disease gene ( GALT ) fail to grow in the presence of even small amounts of galactose due to accumulation of the same toxic intermediates that poison human cells. (genetics.org)
• In general de novo mutations in the foetus and paternally transmitted disorders are less difficult to diagnose than maternally transmitted disorders. (clinicaltrials.gov)
• The investigators will contribute to literature by confirming earlier published results, and by adding other single-gene disorders or mutations to the list of disorders for which the possibility of the use of cff DNA will be examined. (clinicaltrials.gov)
• Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. (ommbidblog.com)
• Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.Nat Genet. (ommbidblog.com)
• Flanagan et al report a new monogenic early-onset polyautoimmunity syndrome caused by activating STAT3 mutations. (ommbidblog.com)
• Haploinsufficiency of A20 (HA20) is a newly described autoinflammatory disease caused by loss-of-function mutations in the TNFAIP3 gene. (bvsalud.org)
• Mutations in the GBA gene that encodes the lysosomal enzyme acid β-glucocerebrosidase cause Gaucher disease (GD), the most common lysosomal storage disorder. (atgcchecker.com)
• i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. (genomicsengland.co.uk)
• In 1999 its genetic basis was discovered by identifying disease-causing mutations in the gene encoding tumor necrosis factor receptor superfamily member 1A. (bvsalud.org)

Susceptibility10

• 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)

Syndromes14

• Clonal unmasking of a heterozygous mutation through somatic loss of the second allele, the main pathomechanism in inherited tumour predisposition syndromes, is rare in metabolic disorders, but focal congenital hyperinsulinism is a notable exception. (springer.com)
• This Review presents an overview of the molecular basis of SCD, with a focus on monogenic arrhythmia syndromes. (jci.org)
• Bona fide lupus syndromes have been associated to this genetic condition, driven by defective nucleic acids metabolism or innate sensors overactivity. (meta.org)
• However, when acute and chronic infections have been excluded and when the fever pattern becomes recurrent or periodic, the expanding spectrum of autoinflammatory diseases, including periodic fever syndromes, should be considered. (cfp.ca)
• Conclusion Periodic fever syndromes and other autoinflammatory diseases are increasingly recognized in children and adults, especially as causes of recurrent fevers. (cfp.ca)
• Currently recognized monogenic syndromes represent a small subset of all epilepsies. (mhmedical.com)
• Numerous gene loci have now been identified for some common seizure patterns and syndromes, many of which are recognized to comprise multiple, genetically distinct diseases. (mhmedical.com)
• Monogenic autoimmunity syndromes are a rare cause of very early-onset multiple autoimmune manifestations. (ommbidblog.com)
• One would intuitively expect that Whole-exome sequencing (WES) will help broaden the phenotypic spectrum of known syndromes since in the past only patients closely matching the described phenotype of a documented genetic syndrome would be tested for the respective diagnosis. (ommbidblog.com)
• Periodic fever syndromes (PFS) are a group of rare autoinflammatory diseases characterized by inappropriate, uncontrolled, and often spontaneous signs and symptoms of inflammation. (psychiatryadvisor.com)
• This study involves the review of the various literatures on orofacial clefts, discussing the problems on the genetic basis, associated syndromes, and their management. (sjclinmed.org)
• AVCD is a very heterogeneous malformation that can occur as a phenotypical cardiac aspect in the context of different genetic syndromes but also as an isolated, non-syndromic cardiac defect. (biomedcentral.com)
• This review attempts to examine the recent advances in understanding the molecular basis of this complex CHD in the setting of genetic syndromes or in non-syndromic patients. (biomedcentral.com)
• Skin symptoms include the main features of monogenic inflammasomopathies, such as Cryopyrin-Associated Periodic Syndromes (CAPS), Familial Mediterranean Fever (FMF), Schnitzler Syndrome, Hyper-IgD Syndrome (HIDS), PAPA Syndrome, and Deficiency of IL-1 Receptor Antagonist (DIRA). (bvsalud.org)

Gene46

• Somatic mosaicism for an OTC gene mutation is given as an example of an apparently heterozygous mutation pattern in a boy with an X-linked disease. (springer.com)
• Beyond screening for chromosomal abnormalities: Advances in non-invasive diagnosis of single gene disorders and fetal exome sequencing. (cdc.gov)
• Non-invasive prenatal diagnosis of single-gene disorders from maternal blood. (cdc.gov)
• Herein, we highlight studies that have identified 26 additional monogenic gene defects that reach the threshold to represent novel causes of immune defects. (bvsalud.org)
• In the absence of gene-environmental studies (such as family-based monozygotic and dizygotic twin studies), estimates of genetic and environmental contributions to disease phenotypes and the interactions between the two are difficult to partition and quantify. (jci.org)
• Dr. Maria Grazia Roncarolo is a pioneer in cell and gene therapy for genetic diseases and a world-renowned expert in immune regulation. (stanford.edu)
• This milestone in gene therapy was integral in the implementation of stem cell and gene therapies for other severe inherited diseases, including Wiskott-Aldrich syndrome (WAS) and metachromatic leukodystrophy (MLD). (stanford.edu)
• As the founder of the CDCM, Dr. Roncarolo continues to lead clinical translation of cell and gene therapy approaches aimed at curing patients with incurable diseases. (stanford.edu)
• Some types of recessive gene disorders confer an advantage in certain environments when only one copy of the gene is present. (wikipedia.org)
• A single-gene (or monogenic ) disorder is the result of a single mutated gene. (wikipedia.org)
• Over 6000 human diseases are caused by single-gene defects. (wikipedia.org)
• Single-gene disorders can be passed on to subsequent generations in several ways. (wikipedia.org)
• When a couple where one partner or both are sufferers or carriers of a single-gene disorder wish to have a child, they can do so through in vitro fertilization, which enables preimplantation genetic diagnosis to occur to check whether the embryo has the genetic disorder. (wikipedia.org)
• Only one mutated copy of the gene will be necessary for a person to be affected by an autosomal dominant disorder. (wikipedia.org)
• Two copies of the gene must be mutated for a person to be affected by an autosomal recessive disorder. (wikipedia.org)
• Two unaffected people who each carry one copy of the mutated gene have a 25% risk with each pregnancy of having a child affected by the disorder. (wikipedia.org)
• The Gene Box (TGB) is India's first holistic health platform providing cost-effective nutrition and health care solutions and services based on wide-ranging genetic analytics. (indiainfoline.com)
• The project will investigate the key mechanisms of new monogenic defects causing immunodeficiency with predominant autoimmunity/autoinflammation, including network approaches, detailed dissection of disease mechanisms, and chemical and genetic screens to complement human disease gene discovery and investigating potential routes for therapeutic modulation. (academicpositions.nl)
• 3 Only a fraction of the epilepsies as a whole can be explained by monogenic inheritance, with epilepsy due to a mutation in a single gene that can be detected by genetic testing occurring in about 30% of affected individuals. (geneticseducation.ca)
• I then worked for fifteen years at the San Raffaele Scientific Institute in the Telethon Institute for Gene Therapy (HSR-TIGET), where I focused on dissecting the genetic and immunological basis of primary immunodeficiencies with autoimmune manifestations that might be treated by gene therapy. (stanford.edu)
• Genetic testing strategy (Figure 1) is based on patient's gender, familial history (if any) and putative mode of disease inheritance, and the presence of additional clinical anomalies that may direct the geneticist towards a particular disease gene or occasionally a contiguous gene syndrome. (nature.com)
• Prof Alexander's specific expertise and interests include virus-mediated gene transfer with a focus on target organs including the liver and bone marrow, both of which have immense promise as target organs for the treatment of genetic disease in children. (edu.au)
• His team became the first in Australia to treat a genetic disease (SCID-X1) by gene therapy and are recognised leaders in the establishment of this exciting field in Australia. (edu.au)
• Gene therapy for genetic and acquired diseases of the liver and haematopoietic system. (edu.au)
• Development of a gene therapy approach for X-linked agammaglobulinaemia, the most prevalent primary immune deficiency disorder in man. (edu.au)
• MEDICAL genetics is based on the assumption that the sequence of a gene (or complete genome) can be used to predict an individual's phenotype(s), including traits related to the prevention, diagnosis, and treatment of human disease. (genetics.org)
• The most success in this regard has come from the analysis of monogenic (Mendelian) traits, i.e ., those linked to polymorphisms in a single gene. (genetics.org)
• Thus, monogenic diseases can be viewed as a special class of complex trait in which allelic variation in one gene has an overwhelmingly strong effect over one or more independently inherited modifier gene(s) that exacerbate or ameliorate the primary disease gene's phenotype. (genetics.org)
• Developing a new non-invasive prenatal test for single gene disorders from cell free fetal DNA, retrieved from the mothers blood. (clinicaltrials.gov)
• Rationale: Conventional prenatal diagnosis (PND) for single-gene disorders requires invasive procedures, either chorionic villus sampling between 11 and 14 weeks gestation or amniocentesis after 15 weeks. (clinicaltrials.gov)
• NIPT of single-gene disorders is technically very challenging, due to the predominance of maternal DNA sequences, Some small studies have shown that a very limited number of monogenic genetic disorders can currently be diagnosed in maternal blood. (clinicaltrials.gov)
• In this study, the investigators aim to develop non-invasive targeted molecular analysis using cell free fetal (cff) DNA and cff RNA for single-gene disorders, in pregnant women referred to the departments of Clinical Genetics of Maastricht University Medical Centre (MUMC+) and Radboud University Medical Centre (RUMC) for conventional PND. (clinicaltrials.gov)
• Objective: Developing targeted non-invasive prenatal analysis for single-gene disorders using cff DNA and RNA in maternal plasma. (clinicaltrials.gov)
• This is subsequently confirmed by genetic testing of the ALDH5A1 gene. (rarediseasesnetwork.org)
• The disease locus was assigned to the short arm of chromosome 16 and a positional cloning approach has identified PRRT2 as the underlying disease gene [ 1 - 3 ] PRRT2 encodes "proline-rich transmembrane protein 2" and appears to be required for normal synapse function. (biomedcentral.com)
• Whole-exome sequencing was conducted to identify a possible genetic disorder, which manifested as pathogenic variant nonsense mutation in the TNFAIP3 gene, leading to HA20. (bvsalud.org)
• A novel mutation deep within intron 7 of the GBA gene causes Gaucher disease. (atgcchecker.com)
• In this interview with The Life Sciences Report , David Nierengarten of Wedbush Securities explores gene therapies that actually correct an inborn mutation in human DNA, creating permanent change, actual cures and better lives for patients. (biomedreports.com)
• Right now-and in the foreseeable future-gene therapy is only going to be used in monogenic diseases. (biomedreports.com)
• I don't view RNAi and these other technologies as gene therapies, even though they're working on the genetic level. (biomedreports.com)
• These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). (genomicsengland.co.uk)
• It's assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. (genomicsengland.co.uk)
• In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. (hud.ac.uk)
• Blood levels of amino acids are important biomarkers of disease and are influenced by synthesis, protein degradation, and gene-environment interactions. (biomedcentral.com)
• and 3) multi-omic approaches that allow measurements of intermediate phenotypes closer to gene action and that bridge genome variation with inter-individual differences in disease risk. (biomedcentral.com)
• There are two types of inheritance: the single-gene inheritance where a feature appears as a result of a single gene carried by one parent and the multifactorial inheritance where a feature appears as a result of a number of genetic and nongenetic factors, such as alcohol, drugs, and environmental factors [ 11 ]. (sjclinmed.org)

Clinical36

• 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)

Metabolism3

• The definition of an inborn error of metabolism is arbitrary. (iospress.com)
• Studies the regulation of cellular metabolism in the context of cancer and genetic disorders. (rockefeller.edu)
• Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited disorder of GABA metabolism characterized by developmental delays and neurologic abnormalities that appear in infancy. (rarediseasesnetwork.org)

Mechanisms12

• Pasteur's germ theory of disease initially seemed to have resolved the long-standing antagonism between the proponents of intrinsic and extrinsic disease mechanisms. (pnas.org)
• Our current understanding of the mechanisms responsible for SCD has emerged from decades of basic science investigation into the normal electrophysiology of the heart, the molecular physiology of cardiac ion channels, fundamental cellular and tissue events associated with cardiac arrhythmias, and the molecular genetics of monogenic disorders of heart rhythm. (jci.org)
• reports on novel research on the genetic mechanisms underlying neurological disorders. (jbcgenetics.com)
• The mechanisms responsible for the development of fibrosis in the lung can be generalized to diseases that lead to fibrosis of other organs ( Figure 1 ). (jci.org)
• This is partly due to the constant improvement of genetic techniques (eg, next-generation sequencing, whole exome and whole genome sequencing) and better understanding of the pathophysiological mechanisms of these diseases. (healio.com)
• The group works at the interface of inborn immune disorders and inherited predisposition to childhood tumors, aiming to understand fundamental mechanisms of immune surveillance relevant to pediatric oncology and immunotherapy approaches. (academicpositions.nl)
• Previous studies of inborn immune defects have enabled discovery of novel disease entities and key biological mechanisms of immune homeostasis (e.g. (academicpositions.nl)
• Our results identified multiple distinct solutions by which the monogenic trait could be suppressed, including genetic and nongenetic mechanisms as well as frequent aneuploidy. (genetics.org)
• He thus characterizes the molecular, cellular, and immunological mechanisms of life-threatening infectious diseases. (rockefeller.edu)
• Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. (nih.gov)
• This process is called reverse cholesterol transport (RCT) and is one of the main mechanisms by which HDL protect against atherosclerotic cardiovascular disease. (clinicaltrials.gov)
• Progress of cellular biology has partially clarified the mechanisms behind monogenic SAIDs, such as familial Mediterranean fever, tumor necrosis factor receptor- associated periodic syndrome, cryopyrin-associated periodic syndrome, mevalonate kinase deficiency, hereditary pyogenic diseases, idiopathic granulomatous diseases and defects of the ubiquitin-proteasome pathway. (mjhid.org)

Mendelian4

• While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. (genetics.org)
• We examined the genetic architecture of monogenic trait modifiers using a well-characterized yeast model of the human Mendelian disease classic galactosemia. (genetics.org)
• Feramisco JD, Sadreyev RI, Murray ML, Grishin NV, Tsao H. Phenotypic and genotypic analyses of genetic skin disease through the online mendelian inheritance in man (OMIM) database. (springer.com)
• Conventional wisdom holds that common complex diseases are polygenic and rare Mendelian diseases are monogenic. (biomedcentral.com)

Infectious Diseases10

• Infectious diseases killed half of all children before the age of 15 y, but this enormous burden was caused by the dazzling diversity of pathogens rather than by the potency of individual pathogens. (pnas.org)
• The key problem concerning pediatric infectious diseases thus was identified: their pathogenesis. (pnas.org)
• The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. (pnas.org)
• According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. (pnas.org)
• Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. (pnas.org)
• For this Inaugural Article, I decided to deviate from the standard approach of providing an extensive review of the work carried out in my laboratory over the last 20 y or in the field of human genetics of infectious diseases more generally since the start of the 20th century. (pnas.org)
• Our specialists are recognized authorities in the diagnosis and treatment of infectious diseases in children and adults. (utswmed.org)
• This work provides theoretical and experimental support for a human genetic theory of severe infectious diseases. (rockefeller.edu)
• Dr. Serkan Belkaya, St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, 1230 York Avenue, Box 163, New York, New York 10065-6399. (onlinejacc.org)
• Here, we show that, similar to the gastrointestinal tract, the mammary gland develops immune and microbial environments consisting of immunoglobulin A (IgA) and the microflora, respectively, both of which are important for protecting neonates and the mother from infectious diseases. (readbyqxmd.com)

20192

• Doyle and Campbell 2019) confirming the ability of influenza to cause fatal disease in a small group of individuals. (clarkfrancis.com)
• Why to attend Metabolic Diseases 2019 Conference? (conferenceseries.com)

Inherited in an autosomal recessive2

• Genetic counseling should be provided, even though most IEMs, except for mitochondrial diseases, are inherited in an autosomal recessive manner. (biomedcentral.com)
• Primary hyperoxaluria type 2 is a rare monogenic disorder inherited in an autosomal recessive pattern. (biomedcentral.com)

Heterogeneous4

• This is a clinically and genetically heterogeneous disease. (nature.com)
• KS is a genetically heterogeneous developmental disease that most often manifests as absent spontaneous puberty combined with a defective sense of smell (hyposmia or anosmia). (nature.com)
• Taken together, our results imply that the modifiers of monogenic traits are likely to be genetically complex and heterogeneous. (genetics.org)
• Hereditary autoinflammatory disorders are a range of heterogeneous conditions that have as a common feature the appearance of unprovoked inflammatory attacks, which may be systemic or occur in localized niches of the body. (bvsalud.org)

Group of monogenic1

• Severe combined immunodeficiency (SCID) includes a group of monogenic disorders presenting with severe T cell lymphopenia (TCL) and high mortality, if untreated. (bvsalud.org)

Mutation5

• Alonso R, Mata N, Castillo S, et al (2008) Cardiovascular disease in familial hypercholesterolaemia: influence of low-density lipoprotein receptor mutation type and classic risk factors. (springer.com)
• Autosomal dominant conditions sometimes have reduced penetrance , which means although only one mutated copy is needed, not all individuals who inherit that mutation go on to develop the disease. (wikipedia.org)
• This blog is intended to create discussion that leads to a better understanding of diseases of human mutation. (ommbidblog.com)
• Line-drawing around seriousness is not determined solely by the identification of a genetic mutation. (unboundmedicine.com)
• 2014. GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding, self-association and cellular degradation. (uib.no)

Abstract1

• 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)

Genetics10

• Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders. (frontiersin.org)
• prenatal diagnosis and the genetics of prenatal and perinatal death, birth defects, perimplantation genetic screening (PGS) and perimplantation genetic diagnosis (PGD). (jbcgenetics.com)
• The journal will also report on animal models of human genetic disorders, ethical, legal and social issues, fetal genetic pathology and teratology, genetic drift, historical aspects of medical genetics, and studies of twins and twinning. (jbcgenetics.com)
• There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. (meta.org)
• UT Southwestern is a leader in both genetics research and the treatment of genetic disorders. (utswmed.org)
• Nature Reviews Genetics 7, 261-276 (April 2006) Focus on: Monogenic disorders Genetic medicines: treatment strategies for hereditary disorders Timothy P. O'Connor and Ronald G. Crystal This great review focuses on the barriers to overcome for the effective treatment of monogenic disorders in the years to come. (ommbidblog.com)
• This study is designed to explore the genetics and pathophysiology of diseases presenting with intermittent fever, including familial Mediterranean fever, TRAPS, hyper-IgD syndrome, and related diseases. (clinicaltrials.gov)
• Genetics and Pathophysiology of Autoinflammatory Disorders. (clinicaltrials.gov)
• The purpose of this protocol is to study the genetics and pathophysiology of familial Mediterranean fever (FMF) and other related diseases. (clinicaltrials.gov)
• I was a fellow in medical genetics 20 years ago when I read the paper wrote by Prof. Jaeken on this new, rare disease. (apcdg.com)

Variants10

• 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)

Severe8

• 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)

Abnormalities7

• The extracted blood can then be used to detect certain anomalies including chromosome abnormalities such as Down Syndrome, blood disorders such as Fetal Haemolytic Disease and intrauterine infection, growth retardation, and some birth defects as well as metabolic disorders. (edu.au)
• A genetic disorder is a genetic problem caused by one or more abnormalities in the genome. (wikipedia.org)
• McKusick's catalog [ 6 ] contains several thousand diseases and disease states whose genetic abnormalities are described or assumed. (iospress.com)
• This disturbance is caused by genetic or environmental factors (including toxic products, congenital infections, nutritional deficiencies, trauma) and may originate either an isolated disability in mental function (non-syndromic MR, or nonspecific MR), or a disorder where a broad range of developmental systems is affected (syndromic MR), resulting in associated physical and functional abnormalities. (scielosp.org)
• PAX2- related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. (nih.gov)
• Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). (hud.ac.uk)
• Conclusion: The article is an attempt to understand the abnormalities associated with cleft lip and cleft palate at genetic level. (sjclinmed.org)

Underlie2

• Genetic lesions might underlie such susceptibilities. (onlinejacc.org)
• Objectives This study sought to evaluate the hypothesis that human genetic factors may underlie AVM in previously healthy children. (onlinejacc.org)

Syndrome10

• It is almost 100% accurate in detecting the presence of genetic and chromosomal disorders such as Down syndrome and Edwards Syndrome. (edu.au)
• Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. (meta.org)
• Familial Mediterranean fever is the most common inherited monogenic autoinflammatory syndrome, and early recognition and treatment can prevent its life-threatening complication, systemic amyloidosis. (cfp.ca)
• Her post-doc project involved characterization of a knock-out mouse model for Mulibrey nanism, a monogenic multi-organ syndrome belonging to the Finnish disease heritage. (fimm.fi)
• Examples of this type of disorder are Huntington's disease , neurofibromatosis type 1 , neurofibromatosis type 2 , Marfan syndrome , hereditary nonpolyposis colorectal cancer , hereditary multiple exostoses (a highly penetrant autosomal dominant disorder), Tuberous sclerosis , Von Willebrand disease , and acute intermittent porphyria . (wikipedia.org)
• Examples of this type of disorder are Albinism , Medium-chain acyl-CoA dehydrogenase deficiency , cystic fibrosis , sickle-cell disease , Tay-Sachs disease , Niemann-Pick disease , spinal muscular atrophy , and Roberts syndrome . (wikipedia.org)
• This study identifies a new genetic syndrome caused by the complete lack of signaling of a whole family of GP130-dependent cytokines in humans and highlights the importance of the LIF signaling pathway in pre- and perinatal development. (ox.ac.uk)
• Then, we considered the possibility of other diseases that could cause early onset rashes and abnormal autoantibodies, including autoinflammatory syndrome, monogenic SLE, or complement deficiency, all of which are rare. (bvsalud.org)
• Meckel-Gruber syndrome is a rare ciliopathy characterized by occipital encephalocele and cystic kidney disease. (elsevier.com)
• This observation ranks Meckel-Gruber syndrome as only the 14th disorder to be caused by an L1 insertion among more than 5,000 known human genetic disorders. (elsevier.com)

Deficiency6

• 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)

Features of monogenic1

• 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)

Lysosomal5

• With the addition of GSDs, we deepen our commitment to lysosomal diseases, and by extension, lysosomal biology. (nd.edu)
• Mucopolysaccharidoses (MPS) are rare inherited disorders caused by a deficit of the lysosomal hydrolases involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). (biomedcentral.com)
• Type I sialidosis, a normosomatic lysosomal disease, in the differential diagnosis of late-onset ataxia and myoclonus: An overview. (atgcchecker.com)
• Lysosomal storage diseases (LSDs) are rare to extremely rare monogenic disorders. (atgcchecker.com)
• AbstractCystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). (medworm.com)

Mitochondrial1

• Using mouse models, we investigated the role of IDH3 in retinal disease and mitochondrial function. (biologists.org)

Predisposition2

• 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)

Chromosomal1

• 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)

Diagnosis13

• cfDNA screening and diagnosis of monogenic disorders - where are we heading? (cdc.gov)
• CVID represents an umbrella diagnosis rather than a single disease, probably encompassing multiple genetic disorders, all leading to the failure of B-cell responses. (frontiersin.org)
• The journal highlights fundamental investigations of the pathogenesis of inherited disorders and practical advances in the molecular diagnosis of human disease. (jbcgenetics.com)
• Genetic testing may provide a specific diagnosis for the individual with epilepsy and may end the diagnostic odyssey. (geneticseducation.ca)
• Therefore, a deeper evaluation of specific disease biomarkers becomes necessary to reach an appropriate diagnosis. (biomedcentral.com)
• In conclusion, HA20 should be considered in the differential diagnosis of an infant with an early-onset dominantly inherited inflammatory disease that presents with recurrent oral and genital ulcerations and fluctuating autoantibodies. (bvsalud.org)
• The diagnosis of PAX2 -related disorder is established in a proband with the characteristic renal and/or eye findings by the identification of a heterozygous pathogenic variant in PAX2 by molecular genetic testing . (nih.gov)
• Prenatal diagnosis and preimplantation genetic diagnosis are possible if the pathogenic PAX2 pathogenic variant has been identified in the family. (nih.gov)
• Preimplantation genetic diagnosis: does age of onset matter (anymore)? (unboundmedicine.com)
• The diagnosis and management of monogenic diabetes in children and adolescents. (uib.no)
• Her studies are directed on congenital anomalies and rare diseases: from primary and secondary prevention to diagnosis, from quality assurance of genetic tests to epidemiologic studies through the National Register, from education of health care providers, to information to citizens and empowerment of patients and improvement of their quality of life. (icord2019.org)
• The most important for the diagnosis is the genetic analysis and its prognosis is determined by the appearance of amyloidosis. (bvsalud.org)
• In recent years, significant advances have been achieved in the diagnosis and treatment of this disease, thanks to a better understanding of its pathogenesis. (bvsalud.org)

Pathogenesis6

• The pathogenesis is more complex in the remaining cases, probably involving environment, and somatic genetic or epigenetic changes ( 8 ). (frontiersin.org)
• Genetic investigations of fibrotic diseases, including those of late onset, often yield unanticipated insights into disease pathogenesis. (jci.org)
• A better understanding of disease pathogenesis may lead to more effective therapies aimed at preventing or reversing the scarring process. (jci.org)
• For these sporadic patients, weaker genetic risk alleles contribute to the pathogenesis of fibrosis. (jci.org)
• The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. (hud.ac.uk)
• Whether the seemingly infrequent recognition of L1 insertion in the pathogenesis of human genetic diseases might simply reflect a lack of appropriate detection methods remains to be seen. (elsevier.com)

Pediatric4

• I believe that much can still be learned from the in depth mechanistic studies of pediatric autoimmune diseases. (stanford.edu)
• These include both the classic pediatric-onset conditions and a number of new diseases that can manifest at any age. (oup.com)
• Rituximab Therapy for Multisystem Autoimmune Diseases in Pediatric Patients The Journal of Pediatrics. (jove.com)
• Pubmed ID: 14615729 To evaluate the effects of rituximab (anti-CD20 monoclonal antibody) on the disease course in pediatric patients with multisystem autoimmune diseases. (jove.com)

Early onset3

• 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)

Inflammatory3

• Defects in immune regulation lead to immunopathology such as inflammatory bowel disease or celiac disease. (ox.ac.uk)
• Loss of IL-10 signaling in macrophages (Mφs) leads to inflammatory bowel disease (IBD). (ox.ac.uk)
• Gout, the most prevalent inflammatory arthritis worldwide, is associated with cardiovascular and renal diseases, and is an independent predictor of premature death. (biomedcentral.com)

Exome1

• 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)

Molecular6

• 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 Diseases1

• 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)

Onset3

• 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)

Glycogen3

• Andersen's disease glycogen storage d., type IV . (thefreedictionary.com)
• Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). (biomedcentral.com)
• The PerlQuest project collaboration aims to screen and identify compounds that can be repurposed to treat glycogen storage diseases (GSDs) such as Cori Disease and Pompe Disease. (nd.edu)

Autoimmunity2

• Disorders in the protection system can lead to autoimmunity and/or autoinflammation, as observed in many diseases. (academicpositions.nl)
• In the coming years, I plan to further determine the genetic and immunological basis of diseases with autoimmunity or immune dysregulation in children. (stanford.edu)

Phenotype2

• In recessive X-linked disorders males are affected, while females may be asymptomatic or present with variable and usually mild phenotype, following a mosaic pattern of distribution. (springer.com)
• iii) Phenotype: the rare disease category, as described in the eligibility statement. (genomicsengland.co.uk)

Autoimmune diseases3

• Autoimmune diseases occur as a result of an attack by the immune system on the body's own tissues resulting in damage and dysfunction. (meta.org)
• Discover the latest research on autoimmune diseases here. (meta.org)
• PFS are considered autoinflammatory, not autoimmune, diseases that may or may not have specific triggers. (psychiatryadvisor.com)

Recessive disorder2

• The fetus is at high risk of having inherited a dominant or recessive disorder of his/her affected parent(s). (clinicaltrials.gov)
• SSADHD is an inherited autosomal recessive disorder. (rarediseasesnetwork.org)

Human7

• In the broadest sense, my research interests include understanding all aspects of the role of genetic factors in human health and disease. (hopkinsmedicine.org)
• Human genetic aspects of inborn ear, nose, and throat diseases]. (semanticscholar.org)
• We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. (nih.gov)
• This Review focuses on biologic pathways implicated by human genetic studies of pulmonary fibrosis. (jci.org)
• Casanova JL (2015a) Human genetic basis of interindividual variability in the course of infection. (springer.com)
• The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. (nih.gov)
• Indeed the biology of human health and disease is complex and there is a continuum of genetic architectures. (biomedcentral.com)

Biochemical1

• 5 ] include several hundred diseases with definite biochemical genetic bases. (iospress.com)

Rare diseases5

• 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)

Branched chain ketoac1

• 1:250,000 (many disorders such as Maple Syrup Urine Disease (branched chain ketoaciduria). (iospress.com)

Complex3

• Most commonly, a complex combination of genetic and non-genetic factors leads to a seizure disorder, with a genetic contribution estimated to be present in up to 70% of affected persons. (geneticseducation.ca)
• When examined closely, the division between monogenic and complex traits quickly breaks down. (genetics.org)
• Orofacial clefts (OFCs) are common congenital malformations of the lip, palate, or both caused by complex genetic and environmental factors [ 2 ]. (sjclinmed.org)

Anomalies2

• The genetic analysis of malformations enables us to distinguish four groups of different anomalies: 1. (semanticscholar.org)
• Some non-reproductive non-olfactory anomalies can also be present, depending on the genetic form of the disease. (nature.com)

Spinal muscula2

• 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)

Renal6

• Outcome of end-stage renal disease in patients with rare causes of renal failure. (tripdatabase.com)
• acquired cystic disease of kidney the development of cysts in the formerly noncystic failing kidney in end-stage renal disease . (thefreedictionary.com)
• End-stage renal disease requiring renal transplant is not uncommon. (nih.gov)
• Genetic family cascade screening was performed in 30/62 cases.ResultsEighty-seven percent of patients had bilateral dysplasia, 74% visible bilateral, and 16% unilateral renal cysts at the end of obse. (medworm.com)
• Renal manifestations of ADPKD are gradual cyst development and kidney enlargement ultimately leading to end-stage renal disease. (medworm.com)
• Here, we document a boy with occipital encephalocele, post-axial polydactyly, and multicystic renal disease. (elsevier.com)

Counseling6

• This will help the delivery of precision medicine and facilitate proper genetic counseling. (frontiersin.org)
• Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged. (nih.gov)
• We also perform genetic screenings based on family history and provide counseling for genetic disorders. (utswmed.org)
• Running parallel to the 'provider market', Genetic counseling services are on the rise. (indiainfoline.com)
• They will receive genetic counseling by the study team on the risk of having affected children and be advised of treatment options. (clinicaltrials.gov)
• The scope of this work is to review the topic and discuss the implications of different genetic and environmental factors, which characterize particular categories of familial cases, suggesting a practical classification of familial MR, which is important for epidemiologic studies and also for counseling in the clinic. (scielosp.org)

Spectrum3

• 13. Schmidt L, Kirchner J, Strunz S, Brozus J, Ritter K, Roepke S, Dziobek I. Psychosocial Functioning and Life Satisfaction in Adults With Autism Spectrum Disorder Without Intellectual Impairment . (cra-rhone-alpes.org)
• Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders. (ommbidblog.com)
• Our findings expand the mutational spectrum of this disease. (biomedcentral.com)

Hereditary disease1

• Also called hereditary disease . (thefreedictionary.com)

Primary6

• To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017. (frontiersin.org)
• The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. (frontiersin.org)
• Genetic testing should be an integral part in the management of primary immunodeficiency patients. (frontiersin.org)
• Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. (biomedcentral.com)
• Primary hyperoxalurias (PHs) are a group of rare autosomal recessive inherited diseases. (biomedcentral.com)
• Is Graves' disease a primary immunodeficiency? (biomedcentral.com)