3 NEW MUTATIONS OF THYROID-HORMONE RECEPTOR-BETA ASSOCIATED WITH RESISTANCE TO THYROID-HORMONE

Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) of the human thyroid hormone receptor-beta gene were observ ed in six individuals affected by the syndrome of resistance to thyroi d hormone. All three mutations occurred in a heterozygous pattern and caused the following changes in the mature form of the receptor protei n: Asp(322) to Asn, Glu(333) to Gln, and Lys(443) to Asn, respectively . The first and third point mutations arose in two unrelated families from eastern Sicily, whereas the second concerned an individual from s outhern Calabria, apparently presenting a sporadic form of the resista nce syndrome. The clinical and biochemical features of resistance to t hyroid hormone, both before and after the administration of thyroid ho rmones, highlight the striking intrafamilial heterogeneity in the phen otypical presentation of the syndrome.