New Case of Thyroid Hormone Resistance α Caused by a Mutation of THRA/TRα1

Abstract

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 <i>de novo</i> mutation (c.1183G>T, p.E395X) was found in one allele of the <i>THRA</i> gene. The mutation creates a stop codon, which eliminates the C-terminal helix of the TR<i>α</i>1 receptor for thyroid hormone. The patient has typical symptoms for the resistance to thyroid hormone <i>α</i> (RTH<i>α</i>) genetic disease, but has a normal head circumference. There are now 21 known mutations in <i>THRA</i>. All mutations that alter the C-terminal helix of TR<i>α</i>1 lead to severe forms of RTH<i>α</i>.