title: The virulence gene and clinical phenotypes of osteopetrosis in the Chinese population: six novel mutations of the CLCN7 gene in twelve osteopetrosis families.
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.
authors.affiliation: Metabolic Bone Disease and Genetics Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, 600 Yishan Road, Shanghai, 200233, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Gu
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Yun-Qiu
authors.initials: YQ
authors.lastname: Hu
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Liu
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.forename: Hua
authors.initials: H
authors.lastname: Yue
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Ke
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D015519:Bone Density; D002648:Child; D002675:Child, Preschool; D002681:China; D018118:Chloride Channels / Q000235:genetics*; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D006262:Health; D006579:Heterozygote; D006615:Hip / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D011859:Radiography; D014019:Tissue Donors; D014774:Virulence / Q000235:genetics; D055815:Young Adult
chemical_list: C097540:CLCN7 protein, human; D018118:Chloride Channels