IDENTICAL MUTATIONS IN UNRELATED FAMILIES WITH GENERALIZED RESISTANCE TO THYROID-HORMONE OCCUR IN CYTOSINE GUANINE-RICH AREAS OF THE THYROID-HORMONE RECEPTOR-BETA GENE - ANALYSIS OF 15 FAMILIES
IDENTICAL MUTATIONS IN UNRELATED FAMILIES WITH GENERALIZED RESISTANCE TO THYROID-HORMONE OCCUR IN CYTOSINE GUANINE-RICH AREAS OF THE THYROID-HORMONE RECEPTOR-BETA GENE - ANALYSIS OF 15 FAMILIES
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DOI：
10.1172/jci116474
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发表时间：
1993-06-01
影响因子：
15.9
通讯作者：
REFETOFF, S
中科院分区：
文献类型：
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作者：
WEISS, RE;WEINBERG, M;REFETOFF, S
全身性甲状腺激素抵抗（GRTH）是一种组织对甲状腺激素反应性可变降低的综合征。人类甲状腺激素受体β（TRbeta）基因中的28种不同点突变与GRTH相关。这些突变聚集在TRbeta的T3结合结构域的两个区域（密码子310-347和417-453）中。我们现在报告的点突变的TRbeta基因的另外6个家庭与GRTH和显示，三个突变发生在三个家庭与GRTH，和其他三个突变分别存在于两个家庭。在这15个家庭中，有11个家庭缺乏共同的祖先，可以通过遗传分析来证实。到目前为止确定的38个点突变中的28个，包括发生在一个以上家族中的所有点突变，位于TRbeta基因的胞嘧啶-鸟嘌呤丰富区域。具有相同TRbeta突变的不相关家族的临床和实验室结果差异表明，其他因素的遗传变异性调节甲状腺激素作用的表达。
Generalized resistance to thyroid hormone (GRTH) is a syndrome of variable reduction of tissue responsiveness to thyroid hormone. 28 different point mutations in the human thyroid hormone receptor beta (TRbeta) gene have been associated with GRTH. These mutations are clustered in two regions of the T3 binding domain of the TRbeta (codons 310-347 and 417-453). We now report point mutations in the TRbeta gene of six additional families with GRTH and show that three mutations occurred each in three families with GRTH, and that three other mutations were each present in two families. In 11 of these 15 families, lack of a common ancestor could be confirmed by genetic analysis. 28 of the 38 point mutations so far identified, including all those occurring in more than one family, are located in cytosine-guanine-rich areas of the TRbeta gene. Differences in clinical and laboratory findings in unrelated families harboring the same TRbeta mutation suggest that genetic variability of other factors modulate the expression of thyroid hormone action.