东莞地区35 145例育龄人群脊髓性肌萎缩症携带者筛查的结果分析  

Results of carrier screening for Spinal muscular atrophy among 35145 reproductive-aged individuals from Dongguan region

作　　者：赵颖[1] 娄季武[1] 付有晴 戴韵诗 梁巧仪 孙曼娜[1] 谭钧铷 刘彦慧[1] Zhao Ying;Lou Jiwu;Fu Youqing;Dai Yunshi;Liang Qiaoyi;Sun Manna;Tan Junru;Liu Yanhui(Prenatal Diagnosis Center,Dongguan Institute of Reproduction and Genetics,Dongguan Maternal and Child Health Care Hospital,Dongguan,Guangdong 523112,China)

机构地区：[1]东莞市妇幼保健院东莞市生殖与遗传研究所产前诊断中心,东莞523112

出　　处：《中华医学遗传学杂志》2023年第6期655-660,共6页Chinese Journal of Medical Genetics

基　　金：广东省基础与应用基础研究计划(2020A1515110308);东莞市社会发展科技计划(20211800904772)。

摘　　要：目的对东莞地区育龄人群进行脊髓性肌萎缩症(SMA)的携带者筛查,探讨本地区人群SMN1基因缺失的携带率。方法选取2020年3月至2022年8月在东莞市妇幼保健院接受SMN1基因筛查的表型正常的育龄期男女为研究对象。采用实时荧光定量PCR(qPCR)技术对受试者SMN1基因的第7/8外显子(E7/E8)进行缺失检测,并对夫妻双方均为携带者的家系应用多重连接探针扩增(MLPA)进行产前诊断。结果在35145例筛查者中,SMN1基因第7外显子缺失的携带者635例(E7/E8杂合缺失586例,E7杂合缺失伴E8纯合缺失2例,单纯E7杂合缺失47例),携带率为1.81%(635/35145)。男性携带率为1.59%(29/1821),女性携带率为1.82%(606/33324),2组差异无统计学意义(χ^(2)=0.497,P=0.481)。1例29岁女性为SMN1基因E7/E8纯合缺失,MLPA验证其SMN1基因型为[0∶4]。其家系中有3名[0∶4]基因型成员均未见相关的临床症状。共11对携带者夫妻进行产前诊断,1例[0∶4]基因型胎儿被终止妊娠。结论本研究首次确定了东莞地区SMA的人群携带率并对高风险夫妇提供了产前诊断,其结果可为SMA的遗传咨询、产前诊断提供参考,对SMA的出生缺陷防控具有重要的意义。Objective To carry out carrier screening for Spinal muscular atrophy(SMA)in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations.Methods Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects.Deletions of exon 7 and 8(E7/E8)of the SMN1 gene were detected by real-time fluorescence quantitative PCR(qPCR),and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification(MLPA).Results Among the 35145 subjects,635 were found to be carriers of SMN1 E7 deletion(586 with heterozygous E7/E8 deletion,2 with heterozygous deletion E7 and homozygous E8 deletion,and 47 with sole heterozygous E7 deletion).The carrier frequency was 1.81%(635/35145),with 1.59%(29/1821)in males and 1.82%(606/33324)in females.There was no significant difference between the two genders(χ^(2)=0.497,P=0.481).A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8,and was verified to have a SMN1∶SMN2 ratio of[0∶4],none of her three family members with a[0∶4]genotype had clinical symptoms.Eleven carrier couples had accepted prenatal diagnosis,and one fetus was found to have a[0∶4]genotype,and the pregnancy was terminated.Conclusion This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples.The data can provide a reference for genetic counseling and prenatal diagnosis,which has important clinical implications for the prevention and control of birth defects associated with SMA.

关 键 词：脊髓性肌萎缩症 SMN1基因 实时荧光定量PCR 多重连接探针扩增 携带者筛查 成人 

分 类 号：R746.4[医药卫生—神经病学与精神病学]