假肥大型肌营养不良症新生儿基因筛查  

Genetic screening in neonates with pseudohypertrophy muscular dystrophy

作　　者：孙云[1] 王欣[1] 管贤伟 张志蕾 张菁菁[1] 洪冬洋 蒋涛[1] Sun Yun;Wang Xin;Guan Xianwei;Zhang Zhilei;Zhang Jingjing;Hong Dongyang;Jiang Tao(Genetic Medicine Center,Women's Hospital of Nanjing Medical University(Nanjing Maternity and Child Health Care Hospital),Nanjing 210004,China)

机构地区：[1]南京医科大学附属妇产医院(南京市妇幼保健院)遗传医学中心,南京210004

出　　处：《中华围产医学杂志》2024年第6期504-510,共7页Chinese Journal of Perinatal Medicine

基　　金：国家自然科学基金(32100680);南京市卫生科技发展专项资金(YKK21159)。

摘　　要：目的分析假肥大型肌营养不良症新生儿基因筛查结果,了解本地区发病情况和热点变异。方法选择2022年3月18日至2023年10月31日于南京医科大学附属妇产医院出生的22813例新生儿(男性12065例,女性10748例),应用芯片捕获二代测序技术检测Dystrophin基因(DMD基因),并对结果进行生物信息学分析,检出致病变异采用多重连接依赖性探针扩增技术及Sanger测序进行验证,男性疑似患者同时检测血清肌酸激酶水平。本研究采用描述性统计学分析。结果芯片捕获二代测序技术在女性新生儿中检出DMD基因携带者14例(0.013%,14/10748),其中9例完成家系验证:1例为新发变异,5例遗传自母亲,3例遗传自父亲;男性新生儿中检出疑似患者9例(0.075%,9/12065),其中8例完成家系验证:3例为新发变异,5例遗传自母亲。检出的DMD基因所有变异类型中,缺失变异最常见,占52.2%(12/23),其中49~51号外显子缺失最多(4例)。结论基于芯片捕获二代测序技术结合生物信息学分析的新生儿基因筛查方案有助于早期发现假肥大型肌营养不良症患者及DMD基因携带者。初步统计本地区假肥大型肌营养不良症的发病率为1/1341男婴,热点变异为49~51号外显子缺失。Objective To understand the regional prevalence and hotspot mutations through analysis of genetic screening results for newborns with pseudohypertrophic muscular dystrophy.Methods A total of 22813 newborns(12065 males and 10748 females)born at the Women's Hospital of Nanjing Medical University from March 18,2022,to October 31,2023,were selected.The Dystrophin gene(DMD)was detected using chip capture next-generation sequencing technology,followed by bioinformatics analysis.Pathogenic mutations identified were validated using multiplex ligation-dependent probe amplification(MLPA)and Sanger sequencing.Serum creatine kinase levels were also tested in suspected male patients.Descriptive analysis was applied for this study.Results Among the 10748 girls,14 carriers of DMD gene were detected(0.013%),of which,nine cases were validated in the family;one case was a de novo mutation,five were inherited from the mother,and three were inherited from the father.The screening identified nine suspected patients among the boys(0.075%),and eight of them were confirmed by family validation,in which three were de novo mutations,and five were inherited from the mother.Among all identified DMD mutations,deletions were the most common one,accounting for 52.2%(12/23),incluling four cases of deletion at 49-51 exon.Conclusions Newborn genetic screening based on chip capture next-generation sequencing technology combined with bioinformatics analysis is helpful in early detection of patients and carriers of pseudohypertrophy muscular dystrophy.According to the preliminary statistics,the incidence rate of DMD/BMD in this area is 1/1341 male infants and the hotspot mutation is exon 49 to 51 deletion.

关 键 词：假肥大型肌营养不良症 新生儿基因筛查 DYSTROPHIN基因 携带者 

分 类 号：R722.1[医药卫生—儿科]