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.

Keywords: Dysmorphism; Founder Mutation; Gujarat; Hair changes; India; Liver hemangiomas; Phenotypic diarrhea; Syndromic diarrhea.

Fig. 1

Dysmorphic facial features of patient 1.

Fig. 2

Light microscopic examination of the hair of patient 1.

Fig. 3

Inverted figure of Ethidium bromide stained 2% Agarose gel showing TTC37 c.2808G>A gene mutation after digestion with Hinf1 restriction enzyme and the chromatogram with altered sequence.