title: A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism.
abstract: 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.
authors: Department of Endocrinology, Research Center of Tissue Engineering, Department of Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. qiaoj2001@126.com
authors: Jie
authors: J
authors: Qiao
authors: Bing
authors: B
authors: Han
authors: Bing-Li
authors: BL
authors: Liu
authors: Xia
authors: X
authors: Chen
authors: Ying
authors: Y
authors: Ru
authors: Kai-Xiang
authors: KX
authors: Cheng
authors: Fu-Guo
authors: FG
authors: Chen
authors: Shuang-Xia
authors: SX
authors: Zhao
authors: Jun
authors: J
authors: Liang
authors: Ying-Li
authors: YL
authors: Lu
authors: Jin-Feng
authors: JF
authors: Tang
authors: Yi-Xin
authors: YX
authors: Wu
authors: Wan-Ling
authors: WL
authors: Wu
authors: Jia-Lun
authors: JL
authors: Chen
authors: Ming-Dao
authors: MD
authors: Chen
authors: Huai-Dong
authors: HD
authors: Song
mesh_terms: D044466:Asian People; D001483:Base Sequence; D002648:Child; D012734:Disorders of Sex Development / Q000235:genetics*; D005190:Family; D005260:Female; D006579:Heterozygote; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D011487:Protein Conformation; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics* / Q000378:metabolism
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; D011974:Receptors, LH