一个遗传性多发性骨软骨瘤家系EXT2基因的突变分析  

Mutation analysis of EXT2 gene in a family with hereditary multiple exostosis

作　　者：李琳[1] 李骁[2] 刘永超[3] 郑书琪[1] 张继霞[1] 刘奇迹[3] 衡雪源[1] 

机构地区：[1]山东省临沂市人民医院遗传研究所,276003 [2]山东省临沂市人民医院骨科 [3]山东大学医学院遗传系

出　　处：《中华医学遗传学杂志》2014年第6期743-746,共4页Chinese Journal of Medical Genetics

基　　金：山东省自然科学基金联合专项（ZR2012CL10）

摘　　要：目的对1个遗传性多发性骨软骨瘤（hereditary multiple exostosis, HME）家系候选致病基因EXTj和EXT2的编码序列进行突变分析，寻找该HEM家系的致病突变，为HME疾病的研究提供分子遗传学证据。方法对山东临沂1个HEM家系进行调查，并进行临床体格检查及影像学检查。提取家系成员外周血DNA，应用PCR技术扩增EXTl、EXT2的全部编码序列并进行直接测序分析。结果该HME家系呈常染色体显性遗传。EXTl、EXT2外显子测序结果显示，该家系中6例患者EXT2基因第2外显子均存在e．244delG杂合缺失突变，导致移码突变从而产生一个只有110个氨基酸的EXT2截短蛋白（P．Asp81 IlefsX30），而正常个体未出现该突变，即家系中该突变与疾病共分离。结论EXT2基因e．244delG突变是导致该家系的致病原因。Objective To investigate EXT1 and EXT2 genes mutations in a family with hereditary multiple osteochondromas （HME）. Methods A four-generation family with HME from Linyi city of Shandong Province was studied. There were 6 affected individuals among the 17 family members. Physical examination and radiographical evaluations were carried out for all family members. Genomic DNA was extracted from peripheral venous blood and the samples were subjected to mutation screening by PCR of the coding regions of EXT1 and EXT2 genes. Results The family has featured an autosomal dominant inheritance pattern. Sequencing of the EXT1 and EXT2 genes suggested the causative gene in this family was in linkage with the second exon of EXT2. A c. 244delG mutation was detected, which has resulted in a frameshift mutation p. Asp81IlefsX30. The mutation was found in all of the 6 affected individuals but not in normal family members. And the mutation has co-segregated with the phenotype. Conclusion The mutation c. 244delG in the EXT2 gene is the probably the cause of the disease in this family.

关 键 词：遗传性多发性骨软骨瘤 EXT2基因 移码突变 

分 类 号：R738.3[医药卫生—肿瘤]