We found a sporadic case of mental retardation associated with short stature and constipation. We investigated the possible genetic origin of the syndrome. Clinical and biochemical investigations were conducted. Exome sequencing was used to search for pathogenic variations. A de novo mutation (c.1183G>T, p.E395X) was found in one allele of the THRA gene. The mutation creates a stop codon, which eliminates the C-terminal helix of the TRα1 receptor for thyroid hormone. The patient has typical symptoms for the resistance to thyroid hormone α (RTHα) genetic disease, but has a normal head circumference. There are now 21 known mutations in THRA. All mutations that alter the C-terminal helix of TRα1 lead to severe forms of RTHα.
Keywords: genetic disease; nuclear receptor; thyroid hormone.