一例Ⅱ型常染色体显性骨硬化症患者氯离子通道蛋白7基因突变分析

Genetic analysis of a novel mutation resulting in autosomal dominant osteopetrosis II

目的检测1例Ⅱ型常染色体显性骨硬化症患者氯离子通道7（chloride channel7，CLCN7）基因的突变情况，探讨其分子发病机制。方法收集1例骨硬化症患者及100名健康成年人的血液标本，提取基因组DNA，PCR扩增CLCN7基因外显子并对所有外显子及其旁侧内含子序列进行DNA测序分析。结果患者CLCN7基因第25外显子存在c．2460delA缺失突变，导致CLCN7基因784位及其后所有密码子移码突变（Arg784GlyfsX29）。该突变为一新突变，正常人均未检测到该突变。结论CLCN7基因Arg784GlyfsX29移码突变是导致该骨硬化症患者发病的原因。

Objective To analyze potential mutation of chloride channel 7 （CLCN7）gene in a patient with autosomal dominant osteopetrosis II （ADO II ）. Methods Genomic DNA was extracted from peripheral blood samples from the patient and 100 healthy subjects. The DNA was used as template of polymerase chain reaction （PCR） to amplify the exons of CLCNT. Then the PCR products were sequenced to detect the mutation. Results A novel heterozygous deletional mutation （c. 2460delA） was detected in exon 25 of the CLCN7 gene in the patient, which has resulted in substitution of Gly residue for Arg at position 784 of the CLCN7 protein and caused frame shift of the following 28 amino acids （Arg784GlyfsX29）. The same mutation was not found in the healthy subjects. Conclusion The ADO II in the patient probably results from a Arg784GlyfsX29 mutation in the CLCN7 gene.