A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism-猫眼课题宝

DOI：

10.1002/humu.21072

发表时间：

2009-09

期刊：

Human Mutation

影响因子：

3.9

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

J. Qiao;B. Han;Bing-Li Liu;Xia Chen;Ying Ru;Kaixiang Cheng;Fu-guo Chen;Shuang-Xia Zhao;Jun Liang;Ying-li Lu;Jinfeng Tang;Yi-Xin Wu;Wan-ling Wu;Jia-lun Chen;Mingdao Chen;Huai-Dong Song

睾丸间质细胞发育不全（LCH）是一种罕见的男性假两性畸形，由促黄体激素受体基因（LHCGR）失活突变引起。大多数LHGR突变位于编码序列中，导致LH/CG结合或信号转导受损。我们报道了一个中国家系，两个兄弟姐妹（46，XY和46，XX）携带错义突变（c。455 T>C，p. Ile 152 Thr）和剪接位点突变（c. 537 - 3 C>A）。在三维结构模型中对错义突变的计算分析预测，它可能会影响激素和受体之间氢键和分子间接触的分布。与这些发现一致，体外突变体分析显示，人绒毛膜促性腺激素结合和信号转导的显着损害。剪接受体突变（c. 537 - 3 C>A）导致LHCGR mRNA异常剪接，跳过外显子7。这份报告扩大了LHCGR突变的基因型谱，与此基因的分子分析的相关影响。© 2009 Wiley利斯公司

Leydig cell hypoplasia (LCH) is a rare form of male pseudohermaphroditism caused by inactivating mutations in the luteinizing hormone receptor gene (LHCGR). The majority of LHCGR mutations are located in the coding sequence, resulting in impairment of either LH/CG binding or signal transduction. We report a Chinese family with two siblings (46, XY and 46, XX) carrying a missense mutation (c. 455 T>C, p. Ile152Thr) and a splice site mutation (c. 537‐3 C>A). Computational analysis of the missense mutation in the three‐dimensional structural model predicted it might influence the distribution of hydrogen bonds and intermolecular contacts between the hormone and receptor. Consistent with these findings, in vitro mutant analysis revealed a marked impairment of human chorionic gonadotropin binding and signal transduction. The splice‐acceptor mutation (c. 537‐3 C>A) resulted in abnormal splicing of LHCGR mRNA, skipping exon 7. This report expands the genotypic spectrum of LHCGR mutations, with relevant implications for the molecular analysis of this gene. © 2009 Wiley‐Liss, Inc.

A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism

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