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Journal of Bone and Mineral Metabolism

, Volume 30, Issue 3, pp 338–348 | Cite as

The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: six novel mutations of the CLCN7 gene in twelve osteopetrosis families

  • Chun Wang
  • Hao Zhang
  • Jin-Wei He
  • Jie-Mei Gu
  • Wei-Wei Hu
  • Yun-Qiu Hu
  • Miao Li
  • Yu-Juan Liu
  • Wen-Zhen Fu
  • Hua Yue
  • Yao-Hua Ke
  • Zhen-Lin ZhangEmail author
Original Article

Abstract

Osteopetrosis is a heritable bone disorder resulting from a deficiency of or a functional defect in osteoclasts. We aimed to characterize the molecular defects and clinical manifestations in Chinese patients with osteopetrosis by studying 12 unrelated osteopetrosis families. The entire coding region and adjacent splice sites of the CLCN7, TCIRG1, LRP5 and SOST genes were amplified and directly sequenced. X-rays of hip and lumbar spine, bone mineral density and bone turnover markers were examined simultaneously. Family history and fracture history were collected using a questionnaire. Among 12 unrelated families, 10 families were diagnosed with autosomal dominant osteopetrosis type II (ADOII) with 10 probands and 3 affected subjects. Two individuals in the other two families were diagnosed with uncategorized osteopetrosis because no mutations were detected in any of the four studied genes. Eight mutations, including two reported mutations (R767W and E798FS) and six novel mutations (E313K, A316G, R743W, G741R, W127G and S290F), were detected in the CLCN7 gene from 12 living ADOII patients. Among them, R767W and R743W mutations were two common mutations that were each found in 20% of 10 ADOII probands. In CLCN7-related ADOII patients, long bone fractures and elevated serum CK level were two major clinical phenotypes, especially in patients younger than 18 years. Further functional studies of the above eight mutations in the CLCN7 gene are needed in the future.

Keywords

Osteopetrosis CLCN7 Mutation Phenotype 

Notes

Acknowledgments

We thank the patients and their family members for their invaluable cooperation. The study was supported by the National Natural Science Foundation of China (NSFC) (No. 30771019, 30800387, 81070692); Program of Shanghai Chief Scientist (Project No. 08XD1403000) and STCSM10DZ1950100; Shanghai Science and Technology Development Fund (Project No. 08411963100 and 11ZR1427300); Shanghai Rising-Star program (11QA1404900).

Conflict of interest

The authors have no conflicts of interest.

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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2011

Authors and Affiliations

  • Chun Wang
    • 1
  • Hao Zhang
    • 1
  • Jin-Wei He
    • 1
  • Jie-Mei Gu
    • 1
  • Wei-Wei Hu
    • 1
  • Yun-Qiu Hu
    • 1
  • Miao Li
    • 1
  • Yu-Juan Liu
    • 1
  • Wen-Zhen Fu
    • 1
  • Hua Yue
    • 1
  • Yao-Hua Ke
    • 1
  • Zhen-Lin Zhang
    • 1
    Email author
  1. 1.Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone DiseasesShanghai Sixth People’s Hospital Affiliated with Shanghai Jiao Tong UniversityShanghaiChina

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