一个遗传性多发性骨软骨瘤家系EXT1基因的突变分析  

Identification of a novel EXT1 mutation in a pedigree affected with hereditary multiple exostosis

作　　者：娄桂予 杨科 秦立涛 张玉薇 王红丹 侯巧芳 何淼 廖世秀 

机构地区：[1]河南省人民医院、郑州大学人民医院、河南省医学遗传研究所,郑州450003

出　　处：《中华医学遗传学杂志》2018年第1期92-95,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81270488）;河南省科技攻关项目（172102310296）

摘　　要：目的对1个遗传性多发性骨软骨瘤（hereditary multiple exostosis, HME）家系的先证者进行候选致病基因EXTI和EXT2的所有外显子检测，以寻找该HEM家系的致病性突变。方法应用PCR技术扩增EXT1、EXT2的全部外显子并进行直接Sanger测序分析。结果测序结果显示先证者EXT1基因第4外显子存在e．1202de1T（P．1401Tfs＊2）杂合缺失突变，该突变导致401位后的编码氨基酸发生移码，并在第402位引入终止密码，使EXTl编码的全长746氨基酸组成的蛋白质缩减至由402个氨基酸组成的截短型蛋白。该家系的其他6例患者均存在EXTle．1202delT的杂合移码突变，而表型正常家系成员未检测到该突变，符合基因型一表型共分离。未检测到EXT2基因的可疑突变。结论EXT1c．1202delT杂合移码突变是导致这个HME家系患者发病的分子机制。Objective To detect potential mutations of the EXT1 and EXT2 genes in a pedigree affected with hereditary multiple exostosis （HME）. Methods For a four-generation family with 7 affected individuals from 17 family members,genomic DNA was extracted from peripheral venous blood samples. All exons of the EXT1 and EXT2 genes were screened for potential mutation by PCR and Sanger sequencing. Results A novel heterozygous frameshift mutation c. 1202delT （p. I401Tfs ＊ 2）was found in exon 4 of the EXT1 gene in the proband and the other 6 affected individuals. The same mutation was not detected among the healthy members from the family. The mutation has given rise a truncated EXT1 protein with loss of 345 amino acids. Conclusion A novel frameshift mutation of the EXT1 gene has been identified in a pedigree affected with HME, which has enriched the mutational spectrum of the EXT1 gene and may facilitate genetic counseling and prenatal diagnosis for the family.

关 键 词：遗传性多发性骨软骨瘤 EXT基因 移码突变 

分 类 号：R738.3[医药卫生—肿瘤]