A NOVEL POINT MUTATION OF THYROID-HORMONE RECEPTOR-BETA GENE IN A FAMILY WITH RESISTANCE TO THYROID-HORMONE

Resistance to thyroid hormone (RTH) is characterized by variable tissu e hyporesponsiveness to thyroid hormone caused by mutations of thyroid hormone receptor beta (TR beta) gene. We found a novel point mutation of the TR beta gene in a family (F123) with RTH, a transition of a gu anine to adenine at nucleotide 1215, which replaced the normal Met-310 with Ile. This substitution was found in only one allele of affected family members. In vitvo transcription and translation of this mutant TR beta demonstrated a 12-fold reduction of the affinity for triiodoth yronine (T3) compared with the wild type TR beta. Thyroid function tes ts were similar to a previously reported RTH family (F99) who had a di fferent mutation in the same codon (Thr 310).