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

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 G>A 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. What is known Syndromic diarrhea/tricho‐hepato‐enteric syndrome is caused by alteration of the human SKI Complex There are seven main clinical features (intractable diarrhea of infancy, hair abnormalities, intrauterine growth restriction, facial dysmorphism, immune disorder, liver disease and skin abnormalities) Only one recurrent mutation has been described (TTC37: pTrp936X) What is new The TTC37 mutation Trp1524X is another recurrent mutation, not previously described, found in individuals of Turkish origin This mutation is associated with a milder phenotype compared to the typical form of SD/THE (less need for parenteral nutrition, less IUGR, and a better chance of survival) We suggest that the C‐terminal part of TTC37 has additional functions in the human SKI complex compared to Ski3, the yeast ortholog)