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

  1. Jie Qiao1,‡,*,
  2. Bing Han2,‡,
  3. Bing-Li Liu2,‡,
  4. Xia Chen3,‡,
  5. Ying Ru2,‡,
  6. Kai-Xiang Cheng1,
  7. Fu-Guo Chen1,
  8. Shuang-Xia Zhao2,
  9. Jun Liang4,
  10. Ying-Li Lu1,
  11. Jin-Feng Tang1,
  12. Yi-Xin Wu2,
  13. Wan-Ling Wu1,
  14. Jia-Lun Chen2,
  15. Ming-Dao Chen2,
  16. Huai-Dong Song2,*

Article first published online: 23 JUN 2009

DOI: 10.1002/humu.21072

Issue

Human Mutation

Human Mutation

Volume 30, Issue 9, pages E855–E865, September 2009

Additional Information

How to Cite

Qiao, J., Han, B., Liu, B.-L., Chen, X., Ru, Y., Cheng, K.-X., Chen, F.-G., Zhao, S.-X., Liang, J., Lu, Y.-L., Tang, J.-F., Wu, Y.-X., Wu, W.-L., Chen, J.-L., Chen, M.-D. and Song, H.-D. (2009), A splice site mutation combined with a novel missense mutation of LHCGR cause male pseudohermaphroditism. Human Mutation, 30: E855–E865. doi: 10.1002/humu.21072

Author Information

  1. 1

    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 200011, China

  2. 2

    State Key Laboratory of Medical Genomics, Molecular Medical Center, Shanghai Institute of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

  3. 3

    Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, NanJing 210029, China

  4. 4

    Department of Endocrinology, Central Hospital of Xuzhou, Xuzhou, Jiangsu 221009, China

  1. ‡

    These authors contributed equally to this work.

*Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

  1. †

    Communicated by Bruce Gottlieb

Publication History

  1. Issue published online: 26 AUG 2009
  2. Article first published online: 23 JUN 2009
  3. Manuscript Accepted: 4 JUN 2009
  4. Manuscript Received: 22 FEB 2009

Funded by

  • National Natural Science Foundation Program, People's Republic of China. Grant Number: 30600297

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Keywords:

  • LHCGR;
  • male pseudohermaphroditism;
  • Leydig cell hypoplasia

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. © 2009 Wiley-Liss, Inc.

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