PHENOTYPE DIFFERENCES OF RESISTANCE TO THYROID-HORMONE IN 2 UNRELATEDFAMILIES WITH AN IDENTICAL MUTATION IN THE THYROID-HORMONE RECEPTOR-BETA GENE (R320C)

A new family with resistance to thyroid hormone (RTH) harboring a muta tion in the thyroid hormone receptor (TR) beta gene (R320C) is reporte d. The phenotype of affected members is compared to that of affected m embers of an unrelated family with an identical mutation in the TRP ge ne that occurred independently. In one of the two families higher conc entrations of free T-4 were required to maintain a normal TSH level in affected subjects and unaffected first degree relatives but not in re latives by marriage. While this finding suggests that genetic backgrou nd modulated the relative insensitivity to thyroid hormone caused by t he mutant TRP, it is uncertain whether the higher thyroid hormone leve ls prevented the occurrence of hyperactivity and attention deficit.