90个脊髓性肌萎缩家系的遗传学分析

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。

Genetic analysis of 90 families affected with spinal muscular atrophy

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.