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A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism
Author(s) -
Qiao Jie,
Han Bing,
Liu BingLi,
Chen Xia,
Ru Ying,
Cheng KaiXiang,
Chen FuGuo,
Zhao ShuangXia,
Liang Jun,
Lu YingLi,
Tang JinFeng,
Wu YiXin,
Wu WanLing,
Chen JiaLun,
Chen MingDao,
Song HuaiDong
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21072
Subject(s) - missense mutation , biology , exon , splice site mutation , genetics , mutation , rna splicing , microbiology and biotechnology , gene , alternative splicing , rna
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.