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.

Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome

“…Trichohepatoenteric Syndrome (THES) is a rare autosomal recessive disorder characterized by growth restriction, severe infantile diarrhea, trichorrhexis nodosa-like hair morphology, hepatopathy, facial dysmorphism, and immunodeficiency ( 1 – 5 ). While THES1 (MIM 222470) is caused by mutation of the TTC37 gene, THES2 (MIM 614602) results from SKIV2L gene mutations ( 6 – 8 ).…”

Identifying Mutations of the Tetratricopeptide Repeat Domain 37 (TTC37) Gene in Infants With Intractable Diarrhea and a Comparison of Asian and Non-Asian Phenotype and Genotype

“… 1 , 11 , 19 – 23 , 27 The patients lacking either identified bi-allelic TTC37 mutations or clinical descriptions were not included in the analysis. For the patients of Asian ethnicity, there were our 2 Taiwanese cases, and 1 Chinese, 19 1 Cambodian, 19 1 Saudi Arabian, 20 4 Indian, 1 , 21 and 5 Pakistani cases 1 (Table 1 ). All of the cases had intractable diarrhea compatible with characteristic intestinal villous atrophy and facial dysmorphism except for our case 2 who was too young for facial dysmorphism to be obvious.…”

The RNA exosome and RNA exosome-linked disease

“…Exome sequencing of 35 individuals with SD/THES1 from 32 unrelated families identified numerous different mutations in TTC37 (Table 1; Fig. 3C; Supplemental Table S2; Hartley et al 2010;Fabre et al 2011Fabre et al , 2013Kotecha et al 2012;Bozzetti et al 2013;Kammermeier et al 2014;Chong et al 2015;Monies et al 2015;Oz-Levi et al 2015;Rider et al 2015;Lee et al 2016a,b;Kinnear et al 2017). Like SKIV2L mutations, most of the TTC37 mutations introduce premature termination codons or other mutations predicted to cause loss of TTC37 function ( Supplemental Table S2); however, eight missense mutations were identified in 10 affected individuals (Table 1).…”