Disease relevance of Databases, Genetic

• Pseudohypoaldosteronism type 1 (PHA1, OMIM 264350) is an uncommon inherited disorder characterized by salt-wasting and end-organ unresponsiveness to mineralocorticoids [1].
• Lysinuric protein intolerance (LPI; OMIM 222700) is a rare, recessive disorder with a worldwide distribution, but with a high prevalence in the Finnish population; symptoms include failure to thrive, growth retardation, muscle hypotonia and hepatosplenomegaly [2].
• Hereditary non-polyposis colorectal cancer (HNPCC; OMIM 120435-6) is a cancer-susceptibility syndrome linked to inherited defects in human mismatch repair (MMR) genes [3].
• Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects [4].
• Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes [5].

Psychiatry related information on Databases, Genetic

• Seckel syndrome (OMIM 210600) is an autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly and mental retardation [6].

High impact information on Databases, Genetic

• Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans [7].
• Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7) [8].
• Silver-Russell syndrome (SRS, OMIM 180860) is a congenital disorder characterized by severe intrauterine and postnatal growth retardation, dysmorphic facial features and body asymmetry [9].
• Most individuals affected with hereditary hemochromatosis are homozygous with respect to a missense mutation that disrupts the conformation of HFE, an atypical HLA class I molecule (ref. 1; OMIM 235200) [10].
• Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals [11].

Chemical compound and disease context of Databases, Genetic

• About 90% of patients with congenital nephrogenic diabetes insipidus are males with the X-linked recessive form of the disease (OMIM 304800) who have mutations in the arginine vasopressin receptor 2 gene (AVPR2), which codes for the vasopressin V2 receptor [12].
• Craniofrontonasal syndrome (CFNS, OMIM 304110) is a distinctive genetic disorder whose main clinical manifestations include coronal synostosis, widely spaced eyes, clefting of the nasal tip and various skeletal anomalies [13].
• This transport system is deficient in the human hereditary lysosomal sialic acid storage diseases (Salla disease and infantile sialic acid storage disease, OMIM 269920) [14].
• Mutations in the genes encoding the subunit polypeptides of the alpha6beta4 integrin (ITGA6 and ITGB4, respectively) have been previously demonstrated in patients with a lethal form of epidermolysis bullosa with congenital pyloric atresia (OMIM #226730) [15].
• Murine succinate semialdehyde dehydrogenase (SSADH) deficiency (OMIM 271980; EC 1.2.1.24), a model of the corresponding human disorder, displays 100% mortality at weeks 3-4 of life, associated with lethal tonic-clonic seizures [16].

Biological context of Databases, Genetic

• Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481) [17].
• Clinically, Seckel syndrome shares features in common with disorders involving impaired DNA-damage responses, such as Nijmegen breakage syndrome (OMIM 251260) and LIG4 syndrome (OMIM 606593) [6].
• Homozygosity for Cst6 null alleles causes the phenotype of the ichq mouse, which is a model for human harlequin ichthyosis (OMIM 242500), a genetically heterogeneous group of keratinization disorders [18].
• Bardet-Biedl syndrome (BBS: OMIM 209900) is a rare developmental disorder that exhibits significant clinical and genetic heterogeneity [19].
• Hereditary fructose intolerance (HFI, OMIM 22960), caused by catalytic deficiency of aldolase B (fructose-1,6-bisphosphate aldolase, EC 4.1.2.13), is a recessively inherited condition in which affected homozygotes develop hypoglycaemic and severe abdominal symptoms after taking foods containing fructose and cognate sugars [20].

Anatomical context of Databases, Genetic

• X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is a genetic disorder characterized by absence or deficient function of hair, teeth and sweat glands [21].
• Missense mutations in the COCH gene, which is expressed preferentially at high levels in the inner ear, cause the autosomal dominant sensorineural deafness and vestibular disorder, DFNA9 (OMIM 601369) [22].
• Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death [23].
• Fish-odor syndrome or Trimethylaminuria (OMIM #602079) in humans is an inborn error of metabolism associated with a characteristic fishy body odor due to elevated levels of trimethylamine (TMA) in body fluids [24].
• Pseudoxanthoma elasticum (PXE; OMIM 177850 and 264800) is a rare heritable disorder of the connective tissue affecting the extracellular matrix of the skin, eyes, gastrointestinal system, and cardiovascular system [25].

Associations of Databases, Genetic with chemical compounds

• Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine [26].
• Hallmarks of the disease are the absence of a creatine signal at brain spectroscopy, increased creatine levels in blood and urine, ineffectiveness of oral supplementation, and a mutation in the SLC6A8 (Online Mendelian Inheritance in Man [OMIM] 300036) creatine transporter gene [27].
• PURPOSE OF REVIEW: Glucose transporter type 1 deficiency syndrome (OMIM 606777) is a treatable epileptic encephalopathy resulting from impaired glucose transport into the brain [28].
• OBJECTIVE: To study the effectiveness of dimethylglycine (DMG) on oxygen consumption (VO(2)) in children with Saguenay-Lac-Saint-Jean cytochrome-c oxidase (SLSJ-COX) deficiency (OMIM 220111) [29].
• The disorder is caused by mutations in NSDHL (Online Mendelian Inheritance in Man 300275), a gene playing an important role in the cholesterol biosynthetic pathway [30].

Gene context of Databases, Genetic

• Hepcidin, a peptide hormone (HAMP; OMIM 606464), seems to act in the same regulatory pathway as HFE [10].
• The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3) [31].
• While a few cases of isolated ACTH deficiency have been reported (OMIM 201400), an inherited POMC defect has not been described so far [32].
• Polycystic liver disease (PCLD, OMIM 174050) is a dominantly inherited condition characterized by the presence of multiple liver cysts of biliary epithelial origin [33].
• Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability [34].

Analytical, diagnostic and therapeutic context of Databases, Genetic

• Sequence analysis confirmed that, in the database genetic background, the presence of two single-nucleotide differences led to two truncated ORFs rather than the full-length FDH2 gene present in strain CEN.PK 113-7D [35].
• Names of specific genes corresponding to the losses or gains on gene map loci were identified from OMIM (Online Mendelian Inheritance in Man) of the NCBI website,. The overexpressions of N-myc and EGFR as well as underexpressions of Rb and ARHI were detected by RT-PCR analysis [36].
• One of these, succinate semialdehyde dehydrogenase (SSADH) deficiency (or gamma-hydroxybutyric aciduria; OMIM 271980; E.C. 1.2.1.24), has recently been modeled via gene targeting in the mouse [37].

References