DMD基因变异特征分析

Analysis of DMD gene variants in a single center

目的了解杜氏肌营养不良症(DMD)和贝氏肌营养不良症(BMD)患者群体的DMD基因变异特点。方法横断面研究,选取2005年1月至2022年2月于郑州大学第一附属医院遗传与产前诊断中心就诊的2690例无亲缘关系的DMD和BMD 0~18岁患儿为研究对象,收集其性别、年龄、临床表现以及地区来源等基本信息并应用多重连接依赖探针扩增、二代测序Panel、Sanger测序及PCR扩增相结合的方法检测其DMD基因的变异情况,对其临床资料及基因检测结果进行描述性分析。结果2690例患儿中男2648例、女42例,年龄6.0(4.0,9.0)岁。所有患儿的血清肌酸激酶值均有异常增高。检测到致病性DMD基因变异的2618例患儿中DMD基因大片段缺失、重复、微小变异分别为1875例(71.6%)、231例(8.8%)和512例(19.6%)。缺失变异中,以3个外显子的缺失最为常见[15.4%(288/1875)],第45~50外显子是最常见的缺失区域[6.3%(119/1875)],第2外显子是最常见的重复区域[13.0%(30/231)]。微小变异在DMD基因的79个外显子上均有分布,无变异热点。此外还检测到46种新发现的微小变异。结论外显子缺失是最常见的DMD基因变异类型,然后依次是微小变异和外显子重复。

Objective To investigate the DMD genetic variants of the Chinese population with Duchenne(DMD)and Becker muscular dystrophies(BMD).Methods A cross-sectional study was conducted on 2690 unrelated patients with DMD and BMD aged 0-18 who visited the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2005 to February 2022.The clinical data,such as gender,age,clinical manifestations,and address,were collected.Multiplex ligation-dependent probe amplification,next generation sequencing panel,Sanger sequencing,and PCR amplification were used to detect the variants of the DMD gene in the patients,whose clinical information and gene detection results were descriptively analyzed.Results The 2690 patients included 2648 males and 42 females,with an age of 6.0(4.0,9.0)years.The serum creatine kinase increased in all patients.Pathogenic DMD gene variants were detected in the 2618 patients,including 1875 cases(71.6%)large deletions,231 cases(8.8%)duplications,and 512 cases(19.6%)small variants.Among the deletion variants,the deletion of 3 exons was the most common,accounting for 15.4%(288/1875);and hotspot deletion involved exons 45 to 50,accounting for 6.3%(119/1875).Exon 2 was the most common type duplication region,accounting for 13.0%(30/231).Small variants were distributed in all 79 exons of the DMD gene,with no hotspots.In addition,the 46 small variants were previously unreported.Conclusion Exon deletion is the most common type of DMD gene variant,followed by small variants and exon duplication.