15年来中国单一中心杜氏/贝氏肌营养不良家系基因突变分析及治疗预期  

Variant analysis and therapeutic prospect for Chinese pedigrees affected with Duchenne/Becker muscular dystrophy from a single center over the past 15 years

作　　者：钟兴健 刘莉娜 孔祥东[1] Zhong Xingjian;Liu Li’na;Kong Xiangdong(Center of Genetic and Prenatal Diagnosis,Department of Gynecology and Obstetrics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产医学部遗传与产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2021年第5期425-429,共5页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002203)。

摘　　要：目的对2005年至2019年15年来中国单中心的2042个无亲缘关系的杜氏/贝氏肌营养不良(Duchenne/Becker muscular dystrophy,DMD/BMD)家系进行DMD基因突变回顾性分析,探讨DMD基因突变在中国汉族人群中的结构特点及相应的期望治疗方案。方法收集2005年1月至2019年8月于本中心就诊的2042个无亲缘关系的DMD/BMD家系,联合应用多重连接探针扩增、二代测序、Sanger测序技术进行DMD基因突变的检测分析。结果2042个中国汉族DMD/BMD家系中,1986个家系检出突变,56个家系未检出变异,检出率为97.26%(1986/2042)。DMD和BMD分别占78.60%和21.40%,其中包括33名女性先证者。大片段缺失、重复和小突变分别占71.85%,8.76%和19.39%。其中,最常见的外显子缺失和重复类型分别是第45~50外显子缺失和第2外显子重复,在小突变中未发现热点。调查了1595个家庭的DMD家族史,遗传率为58.62%(935/1595),新发突变率为41.38%(660/1595)。在本研究中,可以通过已有的基因治疗方法缓解症状的患者比例为34.28%(700/2042)。结论本研究为单中心大样本量的DMD家系突变研究,为97.26%的DMD患者提供了明确分子诊断,为患者家庭的再次生育提供了有效的遗传咨询或产前诊断,丰富了DMD基因的突变谱,为研究DMD基因突变机制及探索DMD的治疗奠定了基础。Objective To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy(DMD/BMD)from a single center from 2005 to 2019.Methods Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification(MLPA),next generation sequencing(NGS)and Sanger sequencing.Results DMD and BMD have respectively accounted for 78.60%and 21.40%of the pedigrees,which included 33 female probands.Variants of the DMD gene were detected in 1986 pedigrees(97.26%).Large deletions,duplications and small-scale mutations have respectively accounted for 71.85%,8.76%and 19.39%.Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2,while no hot spot was found with small-scale mutations.For 1595 pedigrees affected with DMD,935(58.62%)were hereditary and 660(41.38%)were de novo in origin.Thirty-four point two eight percent(700/2042)of the patients had symptoms which could be relieved by gene therapy.Conclusion This has been the largest single-center study of DMD pedigrees,which has attained definite diagnosis in 97.26%of the patients.The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies,enriched the spectrum of DMD gene variants,as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.

关 键 词：杜氏肌营养不良 多重连接探针扩增 二代测序 DMD基因 基因突变 基因治疗 

分 类 号：R746.2[医药卫生—神经病学与精神病学]