微阵列比较基因组杂交在产前诊断中意外检出Duchenne肌营养不良基因变异的回顾性分析  

Unexpected detection of Duchenne muscular dystrophy gene mutation by array comparative genomic hybridization in prenatal diagnosis: a retrospective analysis

作　　者：张倩[1] 吴东[1] 肖海[1] 张秀磊 张梦汀 张波[1] 苏俊祥[1] 刘修铭 李新蕊 廖世秀[1] Zhang Qian;Wu Dong;Xiao Hai;Zhang Xiulei;Zhang Mengting;Zhang Bo;Su Junxiang;Liu Xiuming;Li Xinrui;Liao Shixiu(Institute of Medical Genetics,Henan Provincial People's Hospital,Henan Provincial Key Laboratory of Geneti Diseases and Functional Genomics,Zhengzhou 450003,China;Department of Microbiome Laboratory,Henan Provincial People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院医学遗传研究所,河南省遗传性疾病功能基因组重点实验室,郑州450003 [2]河南省人民医院微生物组实验室,郑州450003

出　　处：《中华围产医学杂志》2021年第8期601-607,共7页Chinese Journal of Perinatal Medicine

基　　金：河南省科技攻关项目(182102310503);河南省医学科技攻关项目(2018020393)。

摘　　要：目的探讨微阵列比较基因组杂交(array comparative genomic hybridization,aCGH)技术对于产前诊断意外检出Duchenne肌营养不良(Duchenne muscular dystrophy,DMD)基因重复/缺失的准确性。方法回顾性分析2018年7月至2019年12月在河南省人民医院5025份无DMD家族史产前诊断样本中,经aCGH检出的31例DMD基因重复/缺失病例。同时使用多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)技术对胎儿及孕妇进行验证,并参考美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)指南对检出DMD基因重复/缺失进行致病性分析。采用描述性方法进行分析。结果31例(0.62%,31/5025)DMD基因重复/缺失中,25例≤200 kb,6例>200 kb;缺失24例,重复7例;外显子重复/缺失19例,内含子重复/缺失12例。对31例变异按照ACMG五分类评分,致病性变异17例,致病不明/可能良性/良性变异14例。检出的19例外显子变异中,17例为DMD基因内部变异,2例涉及DMD基因内部及以外区域变异,经MLPA技术验证,均获得阳性结果。结论aCGH技术检出的DMD基因外显子区域重复/缺失真实可信,对DMD诊断具有重要提示作用。对于同时涉及DMD基因内部及以外区域变异的病例,aCGH能够明确DMD基因上下游断裂点区域,为ACMG分级提供依据。Objective To explore the accuracy of array comparative genomic hybridization(aCGH)in the unexpected detection of Duchenne muscular dystrophy(DMD)gene duplication/deletion in prenatal diagnosis.Methods A retrospective analysis was performed on 31 cases with DMD gene duplication/deletion detected by aCGH among 5025 prenatal diagnosis samples without family history of DMD in Henan Provincial People's Hospital from July 2018 to December 2019.The multiplex ligation-dependent probe amplification(MLPA)method was used to verify the above results.The American College of Medical Genetics and Genomics(ACMG)guideline was referred for pathogenicity analysis of the detected duplicates/deletions.Descriptive analysis was adopted in analysis.Results The total unexpected DMD gene duplication/deletion rate was 0.62%(31/5025),among which 25 cases were with microduplication/microdeletion≤200 kb and six were>200 kb;there were 24 cases of deletion,seven cases of duplication;exon or intron duplication/deletion were accounted for 19 and 12 cases,respectively.According to the five classification standards of ACMG guideline,there were 17 cases with pathogenic variants and 14 cases with uncertain pathogenicity/likely benign variants.Of the 19 with exon mutations,17 cases were DMD intragenic variants,and two cases involved variants in and outside DMD gene,which were verified by MLPA whose results were all positive.Conclusions The duplication/deletion of exon region of DMD gene detected by aCGH technique is accurate and reliable,which plays an important role in the diagnosis of DMD.For these cases involved both internal and external regions of DMD gene,aCGH can identify the upstream and downstream breaking points of DMD gene,thus providing the basis for ACMG grading.

关 键 词：肌营养不良 杜氏 比较基因组杂交 产前诊断 遗传变异 回顾性研究 

分 类 号：R746.2[医药卫生—神经病学与精神病学]