Phenotype differences of resistance to thyroid hormone in two unrelated families with an identical mutation in the thyroid hormone receptor beta gene (R320C).

A new family with resistance to thyroid hormone (RTH) harboring a mutation in the thyroid hormone receptor (TR) beta gene (R320C) is reported. The phenotype of affected members is compared to that of affected members of an unrelated family with an identical mutation in the TR beta gene that occurred independently. In one of the two families higher concentrations of free T4 were required to maintain a normal TSH level in affected subjects and unaffected first degree relatives but not in relatives by marriage. While this finding suggests that genetic background modulated the relative insensitivity to thyroid hormone caused by the mutant TR beta, it is uncertain whether the higher thyroid hormone levels prevented the occurrence of hyperactivity and attention deficit.