云南地区3049名育龄人群脊髓性肌萎缩症携带者筛查结果分析

Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region

目的对云南地区3049名育龄人群进行脊髓性肌萎缩症(spinal muscular atrophy,SMA)的携带者筛查,探讨本地区人群运动神经元存活基因(survival motor neuron,SMN)的拷贝数情况及携带频率。方法应用多重连接探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对SMN1及SMN2基因第7外显子的拷贝数进行检测,筛查出SMN1基因第7外显子拷贝数为1的SMA携带者。对双方均为携带者的夫妇提供产前诊断。结果在3049名育龄人群中,共检测出SMA携带者62例,携带率为1/49(2.03%)。男性携带率为1.91%(40/2094),女性携带率为2.30%(22/955),二者的差异无统计学意义(P>0.05)。SMN1杂合缺失占1.30%(41/3049),由SMN1转换为SMN2者占0.69%(21/3049)。SMN1等位基因的平均拷贝数为1.99。检出双方均为SMA携带者的夫妇2对,通过产前诊断避免了1例患病胎儿的出生。结论云南地区SMA男女携带者的频率无显著差异,符合常染色体隐性遗传模式。阐明SMA携带者的频率和SMN基因的拷贝数情况,可为遗传咨询和产前预防提供依据。

Objective To perform carrier screening for spinal muscular atrophy(SMA)among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron(SMN)gene and carrier frequencies.Methods Multiplex ligation-dependent probe amplification(MLPA)was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene.Prenatal diagnosis was performed for couples whom were both found to be SMA carriers.Results In total 62 SMA carriers were identified among the 3049 subjects,which yielded a carrier frequency of 1 in 49(2.03%).No statistical difference was found in the carrier frequency between males and females(1.91%vs.2.30%,P>0.05).Respectively,1.3%(41/3049)and 0.69%(21/3049)of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene.The average copy number for SMN1 alleles was 1.99.Two couples were found to be both as SMA carriers,for whom the birth of an affected fetus was avoided by prenatal diagnosis.Conclusion No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region,which was in keeping to an autosomal recessive inheritance pattern.Determination of the carrier frequency for SMA and SMN gene variants can provide a basis for genetic counseling and prenatal diagnosis for the disease.