90个脊髓性肌萎缩家系的遗传学分析  

Genetic analysis of 90 families affected with spinal muscular atrophy

作　　者：李涛[1] 吕雪 许泼实[1] 邹杰[1] 肖海[1] 郭谦楠 王红丹 刘红彦 Li Tao;Lyu Xue;Xu Poshi;Zou Jie;Xiao Hai;Guo Qiannan;Wang Hongdan;Liu Hongyan(Department of Medicine Laboratory,Henan Provincial People's Hospital,Central China Fuwai Hospital,Central China Fuwai Hospital of Zhengzhou University,Zhengzhou Henan 450003,China;Department of Health Management,Henan Provincial People's Hospital,Zhengzhou,Henan 450003,China;Medical Genetics Institute,Henan Provincial People's Hospital,Zhengzhou,Henan 450003,China)

机构地区：[1]河南省人民医院、华中阜外医院、郑州大学华中阜外医院医学检验科,郑州450003 [2]河南省人民医院(郑州大学人民医院)健康管理科,郑州450003 [3]河南省人民医院(郑州大学人民医院)医学遗传研究所,郑州450003

出　　处：《中华医学遗传学杂志》2020年第2期116-122,共7页Chinese Journal of Medical Genetics

基　　金：河南省科技攻关计划项目(162102310294,182102310218);河南省医学科技攻关计划项目(201702156,2018020390);河南省卫生计生科技英才海外研修工程(2018151)。

摘　　要：目的对90个脊髓性肌萎缩(spinal muscular atrophy,SMA)家系进行基因诊断与产前诊断,为SMA的遗传学分析方法提供参考,并初步探讨SMA缺陷基因携带者基因筛査的必要性。方法应用多重连接探针扩增(multiplex ligation dependent probe amplification,MLP A)技术对90个SMA家系进行基因诊断,联合MLPA及等位基因特异性PCR(allele specific PCR,A&PCR)技术对家系进行产前诊断并对产前诊断结果进行分析。结果在90个SMA家系中,84对夫妻无SMA家族史,占比93%;85对夫妻有SMA生育史,占比94%;85个家系夫妻双方及3个家系的孕妇SMN1基因杂合缺失,为SMA缺陷基因携带者;2个家系孕妇SMN1基因纯合缺失,为SMA患者;产前诊断结果显示48名胎儿为SMA缺陷基因携带者,23名胎儿为正常胎儿,19名胎儿为SMA患者,其中无家族史夫妻双方再孕SMA胎儿18例,占总SMA胎儿95%、占总胎儿20%。结论应用MLPA对夫妻双方进行SMA缺陷基因携带者筛查,并联合使用MLPA和AS-PCR对携带者夫妻进行SMA产前诊断十分必要,对预防SMA出生缺陷具有积极意义。Objective To carry out genetic testing and prenatal diagnosis for 90 families affected with spinal muscular atrophy(SMA),and discuss the necessity for carrier screening.Methods All families were subjected to multiplex ligation-dependent probe amplification(MLPA)analysis.Combined MLPA and allele-specific PCR(AS-PCR)was used for prenatal diagnosis of the pregnant women.Results Among the 90 couples,84(93%)had a negative family history,85(94%)had given birth to an affected child before.Eighty-five husbands and 88 wives carried heterozygous deletion of exon 7 of the SMN1 gene.Two wives had homozygous deletion of exon 7 of the SMN1 gene and were affected.Prenatal diagnosis showed that 19 fetuses were SMA patients,48 fetuses were carriers,and 23 fetuses were normal.Of note,eighteen affected fetuses were conceived by couples without a family history,which accounted for 20%of all pregnancies and 95%of all affected fetuses.Conclusion To screen SMA carriers using MLPA and carry out prenatal diagnosis using combined MLPA and AS-PCR can ensure accurate diagnosis,which has a significant value for the prevention of SMA affected births.

关 键 词：脊髓性肌萎缩 多重连接探针扩增技术 等位基因特异性PCR 基因诊断 产前诊断 

分 类 号：R74[医药卫生—神经病学与精神病学]