A new mutation in the C‐terminal end of TTC37 TTC37 leading to a mild form of syndromic diarrhea/tricho‐hepato‐enteric syndrome in seven patients from two families

摘要

Syndromic diarrhea/tricho‐hepato‐enteric syndrome (SD/THE) is a rare congenital enteropathy with seven main clinical features: intractable diarrhea of infancy, hair abnormalities, intrauterine growth restriction (IUGR), facial dysmorphism, immune dysfunction, and liver and skin abnormalities. SD/THE is caused by mutations in TTC37 or SKIV2L , two genes encoding components of the human SKI complex. To date, approximately 50 SD/THE patients have been described with a wide spectrum of mutations, and only one recurrent mutation has been identified in independent families. We present a detailed description of seven patients of Turkish origin with the same new mutation in TTC37 : c.4572 GA p.(Trp1524X). All seven patients were homozygous for this mutation and presented the typical clinical features of SD/THE, but with a milder presentation than usual. All seven patients were alive at the last follow‐up. Four out of seven patients had no IUGR, and four patients never required parenteral nutrition. All patients presented a better growth rate than previously described in patients with SD/THE, with 4/7 above the 3rd percentile. The mutation is localized only forty amino acids from the end of TTC37 , and as TTC37 is longer than the yeast SKI3, it is possible that a truncated protein is expressed and plays a reduced role in the SKI complex.