Disease relevance of Genetic Diseases, Inborn

• Mutational inactivation of NER proteins, like DDB and CSA, leads to hereditary diseases such as xeroderma pigmentosum (XP) and Cockayne syndrome (CS) [1].
• Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities [2].
• Homozygous inheritance of the Z-type mutant form of the alpha 1-antitrypsin (alpha 1AT) gene results in the most common form of alpha 1AT deficiency, a human hereditary disease associated with a high risk for the development of emphysema and an increased incidence of neonatal hepatitis [3].
• This procedure is much simpler and cheaper than existing methods and, combined with DNA amplification by polymerase chain reaction, should allow community screening for carrier status for single gene defects such as cystic fibrosis [4].
• Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes [5].

Psychiatry related information on Genetic Diseases, Inborn

• Huntington's disease (HD) is a neurodegenerative and hereditary disease characterized by progressive movement disorders and mental and behavioral abnormalities [6].
• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks (TIA) and strokes, and vascular dementia with Notch3 gene mutations as the cause of the disease [7].
• Tuberous sclerosis is a very infrequent hereditary disease, usually defined by the triad of epilepsy, mental retardation and adenoma sebaceum, although alterations in other organs can exist [8].

High impact information on Genetic Diseases, Inborn

• Macular corneal dystrophy (MCD; MIM 217800) is an autosomal recessive hereditary disease in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantation [9].
• The extensive breakdown of immune homeostasis in the motheaten mouse (me/me) has been ascribed to a single gene defect on chromosome 6 (ref. 1). These mice develop skin lesions within the first week of life, do not thrive, and die within the first 3--8 weeks [10].
• CONTEXT: Gastroesophageal reflux (GER) has not previously been widely regarded as a hereditary disease [11].
• FGFR1 and anosmin-1 may interact via a HSPG dependent mechanism raising the possibility of interaction between two single gene defects cause similar phenotypic abnormalities [12].
• No single gene defect has been firmly associated with MDS/MPDs, and no animal models have been developed for these diseases [13].

Chemical compound and disease context of Genetic Diseases, Inborn

• It also provides quantitative expression data for a variety of genes mutated in hereditary diseases and helps in sorting candidate genes for renal diseases that affect specific portions of the human nephron [14].
• We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance [15].
• The strain also shows sensitivities to x-rays and ultra-violet light, which cosegregate with sensitivity to methyl methanesulfonate as a single gene defect [16].
• Mutations causing expansions of polyalanine domains are responsible for nine hereditary diseases [17].
• Microarrays and polyglutamine disorders: reports from the Hereditary Disease Array Group [18].

Biological context of Genetic Diseases, Inborn

• The receptor gene is located on the avian sex chromosome Z, in agreement with the sex linkage of a single-gene defect in animals that fail to reproduce because of the lack of expression of functional VLDL/VTGR [19].
• Mismatch repair in Escherichia coli enhances instability of (CTG)n triplet repeats from human hereditary diseases [20].
• Saccharomyces cerevisiae rad26 mutants and cells from patients suffering from the hereditary disease Cockayne syndrome display a TCR defective phenotype [21].
• The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations [22].
• Germline mutations in the RET proto-oncogene are responsible for the development of human hereditary diseases, including multiple endocrine neoplasia (MEN) type 2A and 2B, familial medullary thyroid carcinoma (FMTC), and Hirschsprung's disease (HSCR) [23].

Anatomical context of Genetic Diseases, Inborn

• Here we demonstrate that this single gene defect in the restricted-ovulator hen has detrimental consequences for the binding not only of very low density lipoprotein but also of vitellogenin to the 95-kDa receptor normally present in oocytes [24].
• Chronic granulomatous disease (CGD) can result from any of four single gene defects involving the components of the superoxide (O-2) generating phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [25].
• The transforming growth factor beta (TGF-beta) receptor, ALK-1, is expressed specifically on endothelial cells and is essential for angiogenesis, as demonstrated by its targeted deletion in mice and its mutation in the human disease hereditary hemorrhagic telangiectasia [26].
• Hemochromatosis is a hereditary disease characterized by increased absorption of iron from the gastrointestinal tract and deposition of iron in organs [27].
• Cystic fibrosis (CF) is a common, fatal hereditary disease resulting from mutations of the human cystic fibrosis transmembrane conductance regulator (CFTR) gene in which epithelial cells throughout the body manifest altered regulation of apical membrane chloride secretion [28].

Gene context of Genetic Diseases, Inborn

• INTERPRETATION: AME is due to a mutation in the 11 beta-HSD2 gene, and is an example of human hypertension arising from a single gene defect [29].
• A mutation that interferes with proper folding and assembly of HFE complexes results in a severe iron-overload disease hereditary hemochromatosis [30].
• Of nine known human genes in this family, three (SLC26A2, SLC26A3 and SLC26A4) are associated with different human hereditary diseases [31].
• Given that a single gene defect (FMR1) is known to be responsible for this disorder, we also assess whether brain activation in arithmetic processing areas is related to amount of FMR1 protein expression (FMRP) [32].
• Steroid 11 beta-hydroxylase deficiency (11 beta OHD), an autosomal recessive hereditary disease, accounts for 5-8% of cases of congenital adrenal hyperplasia [33].

Analytical, diagnostic and therapeutic context of Genetic Diseases, Inborn

• The survival of these resistant clones, after treatment with cisplatin, was about the same as WR cells a finding which would be consistent with complementation by a transferred gene or reversion of a single gene defect in WS cells [34].
• OBJECTIVE: To describe a laboratory approach to the diagnosis of hereditary diseases of purine and pyrimidine metabolism and emphasize clinical situations in which these disorders should be considered in the differential diagnosis [35].
• When purification of these syncytial fragments can be achieved using immuno-magnetic technology, this test will enable prenatal diagnosis of single gene defects in the fetus by the polymerase chain reaction [36].
• CONCLUSIONS: Human diseases with single-gene defects such as LHON may soon be treated successfully by gene therapy, assuming that vectors continue to improve and are well tolerated in the human eye [37].
• In this article we review approaches which use the multidrug-resistance gene to protect bone marrow from myelosuppression following chemotherapy and as a selectable markerin vivo to increase the expression of nonselectable genes which correct hereditary diseases of the hematopoietic system [38].

References