CHARACTERIZATION OF THE HUMAN GROWTH-HORMONE RECEPTOR GENE AND DEMONSTRATION OF A PARTIAL GENE DELETION IN 2 PATIENTS WITH LARON-TYPE DWARFISM
CHARACTERIZATION OF THE HUMAN GROWTH-HORMONE RECEPTOR GENE AND DEMONSTRATION OF A PARTIAL GENE DELETION IN 2 PATIENTS WITH LARON-TYPE DWARFISM
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DOI：
10.1073/pnas.86.20.8083
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发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
WOOD, WI
中科院分区：
文献类型：
--
作者：
GODOWSKI, PJ;LEUNG, DW;WOOD, WI
Laron型侏儒症是一种常染色体隐性遗传疾病，其特征是循环中高水平的生长激素和低水平的胰岛素样生长因子I。几条证据表明，这种疾病是由生长激素受体缺陷引起的。为了分析Laron型侏儒症和其他生长障碍患者的受体基因，我们首先确定了正常个体的基因结构。有9个外显子编码受体和5“非翻译区中的几个额外的外显子。编码外显子跨越5号染色体的至少87个内切酶对。来自9名Laron型侏儒症患者的生长激素受体基因的表征表明，两个个体具有受体基因的细胞外激素结合结构域的大部分缺失。有趣的是，这种缺失包括非连续的外显子，表明可能发生了不寻常的重排。因此，我们提供了直接的证据表明，Laron型侏儒症可能是由于生长激素受体的结构基因缺陷。
Laron-type dwarfism is an autosomal recessive genetic disorder that is characterized by high levels of growth hormone and low levels of insulin-like growth factor I in the circulation. Several lines of evidence suggest that this disease is caused by a defect in the growth hormone receptor. In order to analyze the receptor gene in patients with Laron-type dwarfism and with other growth disorders, we have first determined the gene structure in normal individuals. There are nine exons that encode the receptor and several additional exons in the 5'' untranslated region. The coding exons span at least 87 kilobase pairs of chromosome 5. Characterization of the growth hormone receptor gene from nine patients with Laron-type dwarfism shows that two individuals have a deletion of a large portion of the extracellular, hormone binding domain of the receptor gene. Interestingly, this deletion includes nonconsecutive exons, suggesting that an unusual rearrangement may have occurred. Thus, we provide direct evidence that Laron-type dwarfism can result from a defect in the structural gene for the growth hormone receptor.