茂名地区育龄妇女脊髓性肌萎缩症SMN1突变携带者筛查与分析

Screening and analysis of SMN1 mutation carriers of spinal muscular atrophy in childbearing age women in Maoming region

目的对茂名地区育龄妇女进行脊髓性肌萎缩症(SMA)运动神经元存活基因1(SMN1)突变携带者筛查,掌握SMA流行病学数据,为SMA家系进行遗传咨询、基因筛查和产前诊断提供依据。方法收集2020年5月-2021年8月在茂名市妇幼保健院进行孕检的1898名妇女临床资料和肘静脉外周血样本。采用MGB探针实时多重荧光定量PCR法,分别对SMN1第7外显子和第8外显子的拷贝数进行相对定量检测,并分析目的基因的缺失情况及携带频率,为男女双方均为阳性携带者的夫妇进行产前诊断。结果在1898名育龄妇女中,共检测出脊髓性肌萎缩症SMN1突变携带者49例,携带率为2.58%;其中SMN1-7杂合缺失/SMN1-8杂合缺失最多33例(1.74%),其次为SMN1-7未见缺失/SMN1-8杂合缺失12例(0.63%)和SMN1-7杂合缺失/SMN1-8未见缺失4例(0.21%)。2对双方均为阳性携带者夫妻的3例胎儿羊水标本中2例为SMN1-7杂合缺失/SMN1-8杂合缺失和SMN1-7杂合缺失/SMN1-8未见缺失,建议继续妊娠;1例为SMN1-7纯合缺失/SMN1-8纯合缺失,建议对胎儿进行终止妊娠。结论茂名地区育龄妇女脊髓性肌萎缩症SMN1突变携带率高于中国南部其他地区,建议采用实时多重荧光定量PCR法对该地区育龄妇女进行SMN1突变筛查及产前诊断,有效减少SMA胎儿的出生。

Objective To analyze the survival motor neuron 1(SMN1)mutation carriers of spinal muscular atrophy(SMA)of childbearing age women in Maoming,and provide basis for genetic counseling,gene screening and prenatal diagnosis of SMA families.Methods Collect clinical data and peripheral blood samples from the elbow vein of 1898 women who underwent pregnancy examinations at Maoming Maternal and Child Health Hospital from May 2020 to August 2021.MGB probe real-time multiplex fluorescence quantitative PCR was used to detect the copy numbers of exon 7 and exon 8 of SMN1,and analyze the deletion and carrying frequency of the target gene,so as to make prenatal diagnosis for couples who were both male and female positive carriers.Results Among 1898 women of childbearing age,49 cases of SMN1 mutation carriers of spinal muscular atrophy were detected,and the carrying rate was 2.58%.Among them,33 cases(1.74%)had SMN1-7 heterozygosity deficiency/SMN1-8 heterozygosity deficiency,12 cases(0.63%)had SMN1-7 not deficiency/SMN1-8 heterozygosity deficiency,4 cases(0.21%)had SMN1-7 heterozygosity deficiency/SMN1-8 not deficiency.Among the 3 fetal amniotic fluid samples of 2 couples who were both positive carriers,2 cases were SMN1-7 heterozygosity deficiency/SMN1-8 heterozygosity deficiency and SMN1-7 heterozygosity deficiency/SMN1-8 not deficiency,that recommends to continue pregnancy,and 1 case was SMN1-7 homozygous deletion/SMN1-8 homozygous deletion;of which,termination of pregnancy was recommended.Conclusions The carrying rate of SMN1 mutation in women of childbearing age in Maoming was higher than that in other regions in southern China.It was suggested that real-time multiplex fluorescence quantitative PCR should be used to screen SMN1 mutation carriers and prenatal diagnosis for fertile women in this area,so as to effectively reduce the birth of SMA fetuses.