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.
['Fabre|Alexandre|A|http://orcid.org/0000-0001-5155-6437', 'Petit|Laetitia-Marie|LM|', 'Hansen|Lars F|LF|', 'Wewer|Anne V|AV|', 'Esteve|Clothilde|C|', 'Chaix|Charlène|C|', 'Bourgeois|Patrice|P|', 'Badens|Catherine|C|', 'Paerregaard|Anders|A|']
D000483:Alleles D002352:Carrier Proteins D002675:Child, Preschool D003967:Diarrhea D005190:Family D005260:Female D005838:Genotype D006801:Humans D007223:Infant D008297:Male D009154:Mutation D010375:Pedigree D010641:Phenotype D035781:Siblings D013577:Syndrome
TTC37 syndromic diarrhea tricho-hepato-enteric syndrome SKIV2L Ski complex Ski3