15例疑似假肥大性肌营养不良患儿遗传学分析  

Genetic analysis on 15 cases of suspected Duchenne muscular dystrophy/Becker muscular dystrophy

作　　者：蔡潇艺 娄丹[2] 杨兴鸽[2] 王剑 CAI Xiaoyi;LOU Dan;YANG Xingge;WANG Jian(School of Clinical Medicine,Henan University of Science and Technology,Luoyang 471003,Henan,China;The First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471003,Henan,China;The International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China)

机构地区：[1]河南科技大学临床医学院,河南洛阳471003 [2]河南科技大学第一附属医院,河南洛阳471003 [3]上海交通大学医学院附属国际和平妇幼保健院,上海200030

出　　处：《检验医学》2023年第2期106-111,共6页Laboratory Medicine

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20200572);河南省中国科学院科技成果转移转化项目(2018105)。

摘　　要：目的分析进行性假肥大性肌营养不良(DMD)患儿的临床特点和基因变异情况,为临床诊断、治疗和遗传咨询提供参考。方法对2019年7月—2021年7月河南科技大学第一附属医院15例疑似假肥大性肌营养不良患儿的临床特征进行回顾性分析,并采用多重连接探针扩增技术(MLPA)和全外显子组测序(WES)分析患儿的基因变异特点。对变异位点进行生物信息学分析。结果15例患儿中,有14例存在DMD基因变异,其中12例为外显子区域大片段缺失,2例为点突变[c.2168+1G>T和c.9917_9923del(p.Thr3306Serfs*22)]。检测到的DMD基因大片段缺失共涉及11个不同的区域,其中8个可引起抗肌萎缩蛋白可读框移码,2个可引起阅读框内整码缺失,1个缺失变异覆盖整个DMD基因。14例DMD基因变异患儿均有酶学异常增高、肌源性损伤等特征,被确诊为DMD。1例未检测到DMD基因变异的患儿存在LAMA2基因复合杂合变异[c.819+1G>A和c.1884G>A(p.Glu628Glu)],被诊断为肢带型肌营养不良(LGMD)。结论临床需注意DMD、贝克肌营养不良(BMD)和LGMD的鉴别诊断,对合并肌酸激酶(CK)等酶学改变和肌源性损伤的进行性肌营养不良患儿,建议优先考虑采用MLPA检测DMD基因外显子拷贝数;对于MLPA检测结果阴性的患儿,采用高通量测序进一步分析其遗传学病因。Objective To analyze the clinical characteristics and gene variation of Duchenne muscular dystrophy(DMD),and to provide a reference for clinical diagnosis,treatment and genetic counseling.Methods The clinical characteristics of 15 children with suspected pseudohypertrophic muscular dystrophy in the First Affiliated Hospital of Henan University of Science and Technology from July 2019 to July 2021 were analyzed retrospectively,and the gene variation characteristics were analyzed by multiplex ligation-dependent probe amplification(MLPA)and whole-exome sequencing(WES).The variation sites were analyzed by bioinformatics.Results Among the 15 patients,14 patients had variations in DMD gene,including 12 large exon deletions and 2 point mutations[c.2168+1G>T and c.9917_9923del(p.Thr3306Serfs*22)].The identified large deletions were involved in 11 different regions of DMD gene,of which 8 caused frameshifts,2 caused in-frame deletions and 1 caused loss of whole protein expression.The 14 patients with DMD gene variations had the characteristics of abnormally increased enzymes and myogenic damage,and they were diagnosed as DMD.In addition,1 patient with negative result from DMD gene detection had compound heterozygous variation of LAMA2 gene[c.819+1G>A and c.1884G>A(p.Glu628Glu)],and the subject was diagnosed with limb-girdle muscular dystrophy(LGMD).Conclusions Clinical attention should be paid to the differential diagnosis of DMD,Becker muscular dystrophy and LGMD.For children with progressive muscular dystrophy combined with creatine kinase and other enzymatic change and myogenic damage,MLPA is recommended to detect the copy number of DMD gene.Next-generation sequencing should be used to further analyze the genetic etiology.

关 键 词：进行性假肥大性肌营养不良 多重连接探针扩增技术 全外显子组测序 基因诊断 

分 类 号：R446.1[医药卫生—诊断学]