A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism.
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.
Qiao
Jie
J
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
Han
Bing
B
Liu
Bing-Li
BL
Chen
Xia
X
Ru
Ying
Y
Cheng
Kai-Xiang
KX
Chen
Fu-Guo
FG
Zhao
Shuang-Xia
SX
Liang
Jun
J
Lu
Ying-Li
YL
Tang
Jin-Feng
JF
Wu
Yi-Xin
YX
Wu
Wan-Ling
WL
Chen
Jia-Lun
JL
Chen
Ming-Dao
MD
Song
Huai-Dong
HD
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
D022821:RNA Splice Sites; D012333:RNA, Messenger; D011974:Receptors, LH