新错义突变生长激素释放激素受体基因家族性孤立GH缺乏。
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Carakushansky M, Whatmore AJ,克莱顿PE、Shalet SM,格里森香港,价格DA,莱文MA, Salvatori发现R
新错义突变生长激素释放激素受体基因家族性孤立GH缺乏。
欧元J性。2003年1月,148 (1):25 - 30。
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12534354 (在PubMed]
- 文摘
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目的:突变GH-releasing激素(GHRH)受体(GHRHR) (GHRHR)导致常染色体隐性基因家族性孤立GH缺乏(IGHD)。我们寻必威国际app找GHRHR突变两兄弟姐妹IGHD IB型和父母的血缘关系的历史。设计:我们分析了外围指数病人的基因组DNA。识别GHRHR的小说突变后,我们进行功能研究,以确认受体突变原因故障。方法:分析了整个GHRHR指数情况下通过变性梯度凝胶电泳。异常迁移乐队是孤立和测序。突变区域测序在所有家庭成员的DNA。新发现的突变是一个GHRHR cDNA插入。野生型和突变体的互补成CHO细胞表达和环腺苷酸(cAMP)对GHRH测量。为了确定突变体受体是否正确表达了在细胞膜表面,CHO细胞转染野生型和突变体GHRHR cDNA包含一个标记抗原决定基标记在细胞外的n端。 RESULTS: Both patients were homozygous for a new missense mutation in codon 176, corresponding to the second transmembrane domain of the receptor protein that replaces alanine with valine (A176V). The mother and three unaffected siblings were heterozygous for the mutation; DNA from the father was not available. Cells expressing the A176V receptor had a significantly reduced cAMP response to GHRH, despite appropriate expression on the cell surface. CONCLUSIONS: We describe two siblings with IGHD due to a new mutation in the GHRHR that disrupts GHRH signaling and leads to GHRH resistance.