Bartolone L, Regalbuto C, Benvenga S, Filetti S, Trimarchi F, Pontecorvi A
Institute of Endocrinology, University of Messina, Rome, Italy.
J Clin Endocrinol Metab. 1994 Jul;79(1):323-6. doi: 10.1210/jcem.79.1.7913092.
Three novel point mutations at nucleotides 1249, 1282, and 1614 (exons 9 and 10) of the human thyroid hormone receptor-beta gene were observed in six individuals affected by the syndrome of resistance to thyroid hormone. All three mutations occurred in a heterozygous pattern and caused the following changes in the mature form of the receptor protein: Asp322 to Asn, Glu333 to Gln, and Lys443 to Asn, respectively. The first and third point mutations arose in two unrelated families from eastern Sicily, whereas the second concerned an individual from southern Calabria, apparently presenting a sporadic form of the resistance syndrome. The clinical and biochemical features of resistance to thyroid hormone, both before and after the administration of thyroid hormones, highlight the striking intrafamilial heterogeneity in the phenotypical presentation of the syndrome.
在六名患有甲状腺激素抵抗综合征的个体中，观察到人类甲状腺激素受体-β基因第1249、1282和1614位核苷酸（外显子9和10）处有三个新的点突变。所有这三个突变均以杂合模式出现，并分别导致受体蛋白成熟形式发生以下变化：Asp322变为Asn、Glu333变为Gln、Lys443变为Asn。第一个和第三个点突变出现在来自西西里岛东部的两个不相关家族中，而第二个突变涉及来自卡拉布里亚南部的一名个体，显然呈现出该抵抗综合征的散发形式。在给予甲状腺激素之前和之后，甲状腺激素抵抗的临床和生化特征突出了该综合征表型表现中显著的家族内异质性。
