Dataset Information

Trichohepatoenteric syndrome: founder mutation in asian indians.

ABSTRACT: Trichohepatoenteric syndrome (THES) is characterized by chronic diarrhea, dysmorphic facies and hair abnormalities. Hepatic involvement varies from no abnormality to cirrhosis and hemochromatosis. Recently, mutations in the tetratricopeptide repeat domain 37 (TTC37) gene were identified to cause THES. The c.2808G>A variation was suggested as a possible founder mutation among the South Asians. We further report 2 unrelated cases of Asian-Indian ethnicity (Gujrati) with THES, wherein targeted mutation analysis revealed the same mutation in homozygous form in both cases. These findings, as well as haplotype analysis, corroborate the founder mutation hypothesis amongst Asian Indo-Pakistani ethnic groups. A restriction enzyme-based method is also described to identify this founder mutation. One of our probands had multiple hepatic hemangiomas, a feature not previously observed in this syndrome.

SUBMITTER: Kotecha UH

PROVIDER: S-EPMC3542929 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Trichohepatoenteric syndrome: founder mutation in asian indians.

Kotecha U H UH Movva S S Puri R D RD Verma I C IC

Molecular syndromology 20120705 2

Trichohepatoenteric syndrome (THES) is characterized by chronic diarrhea, dysmorphic facies and hair abnormalities. Hepatic involvement varies from no abnormality to cirrhosis and hemochromatosis. Recently, mutations in the tetratricopeptide repeat domain 37 (TTC37) gene were identified to cause THES. The c.2808G>A variation was suggested as a possible founder mutation among the South Asians. We further report 2 unrelated cases of Asian-Indian ethnicity (Gujrati) with THES, wherein targeted muta ...[more]

PMID: 23326254

Similar Datasets

Project description:OBJECTIVES: To determine the prevalence of metabolic syndrome and to identify predictors for the same, specific to an underdeveloped urban locale of Eastern India. MATERIALS AND METHODS: STUDY DESIGN: Population-based cross-sectional study, with multistage random sampling technique. SETTING: Urban city-dwellers in Orissa one of the poorest states of Eastern India bordering a prosperous state of Andhra Pradesh of Southern India. PARTICIPANTS: 1178 adults of age 20-80 years randomly selected from 37 electoral wards of the urban city. Definition of Metabolic Syndrome: We followed a unified definition of the metabolic syndrome by joint interim statement of five major scientific organizations - the International Diabetes Federation, the National Heart, Lung, and Blood Institute, the American Heart Association, the World Heart Federation, the International Atherosclerosis Society, and the International Association of the Study of Obesity. Individuals who meet at least three of five clinical criteria of abdominal obesity, hypertriglyceredimia, low HDL, hypertension, and hyperglycemia are diagnosed as having the condition; presence of none of these criteria is mandatory. Explicit cut points are defined for all criteria, except elevated waist circumference, which must rely on population and country-specific definitions. MAIN OUTCOME MEASURE: Prevalence and significant predictors of metabolic syndrome. STATISTICAL ANALYSIS: Both descriptive and multivariable logistic regression analyses. RESULTS: Age-standardized prevalence rates of metabolic syndrome were 33.5% overall, 24.9 % in males and 42.3% in females. Older age, female gender, general obesity, inadequate fruit intake, hypercholesterolemia, and middle-to-high socioeconomic status significantly contributed to increased risk of metabolic syndrome. CONCLUSION: Metabolic syndrome is a significant public health problem even in one of the poorest states of India that needs to be tackled with proven strategies.

Project description:Background & aimsTrichohepatoenteric syndrome (THES) is an autosomal-recessive disorder characterized by life-threatening diarrhea in infancy, immunodeficiency, liver disease, trichorrhexis nodosa, facial dysmorphism, hypopigmentation, and cardiac defects. We attempted to characterize the phenotype and elucidate the molecular basis of THES.MethodsTwelve patients with classic THES from 11 families had detailed phenotyping. Autozygosity mapping was undertaken in 8 patients from consanguineous families using 250,000 single nucleotide polymorphism arrays and linked regions evaluated using microsatellite markers. Linkage was confirmed to one region from which candidate genes were analyzed. The effect of mutations on protein production and/or localization in hepatocytes and intestinal epithelial cells from affected patients was characterized by immunohistochemistry.ResultsPreviously unrecognized platelet abnormalities (reduced platelet alpha-granules, unusual stimulated alpha granule content release, abnormal lipid inclusions, abnormal platelet canalicular system, and reduced number of microtubules) were identified. The THES locus was mapped to 5q14.3-5q21.2. Sequencing of candidate genes showed mutations in TTC37, which encodes the uncharacterized tetratricopeptide repeat protein, thespin. Bioinformatic analysis suggested thespin to be involved in protein-protein interactions or chaperone. Preliminary studies of enterocyte brush-border ion transporter proteins (sodium hydrogen exchanger 2, sodium hydrogen exchanger 3, aquaporin 7, sodium iodide symporter, and hydrogen potassium adenosine triphosphatase [ATPase]) showed reduced expression or mislocalization in all THES patients with different profiles for each. In contrast the basolateral localization of Na/K ATPase was not altered.ConclusionsTHES is caused by mutations in TTC37. TTC37 mutations have a multisystem effect, which may be owing to abnormal stability and/or intracellular localization of TTC37 target proteins.

Dataset Information

Trichohepatoenteric syndrome: founder mutation in asian indians.

Publications

Trichohepatoenteric syndrome: founder mutation in asian indians.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets