A Mutation in the Thyroid Hormone Receptor Alpha Gene
A Mutation in the Thyroid Hormone Receptor Alpha Gene
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DOI：
10.1056/nejmoa1110296
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发表时间：
2012-01-19
影响因子：
158.5
通讯作者：
Chatterjee, Krishna
中科院分区：
文献类型：
--
作者：
Bochukova, Elena;Schoenmakers, Nadia;Chatterjee, Krishna
甲状腺激素通过α（TR α 1）和β（TR β 1和TR β 2）受体发挥作用。在这里，我们描述了一个典型的甲状腺功能减退症的特点（生长迟缓，发育迟缓，骨骼发育不良，严重便秘），但只有边界异常的甲状腺激素水平的儿童。使用全外显子组测序，我们确定了编码甲状腺激素受体α（THRA）的基因中的从头杂合无义突变，并产生一种突变蛋白，以显性负性方式抑制野生型受体作用。我们的观察结果与缺陷型人TR α介导的甲状腺激素抵抗一致，并证实了激素作用通过不同靶组织中不同受体亚型的概念。
Thyroid hormones exert their effects through alpha (TR alpha 1) and beta (TR beta 1 and TR beta 2) receptors. Here we describe a child with classic features of hypothyroidism (growth retardation, developmental retardation, skeletal dysplasia, and severe constipation) but only borderline-abnormal thyroid hormone levels. Using whole-exome sequencing, we identified a de novo heterozygous nonsense mutation in a gene encoding thyroid hormone receptor alpha (THRA) and generating a mutant protein that inhibits wild-type receptor action in a dominant negative manner. Our observations are consistent with defective human TR alpha-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues.