广东佛山地区19297名孕妇脊髓性肌萎缩症携带者筛查及产前诊断

Carrier screening and prenatal diagnosis of spinal muscular atrophy among 19297 pregnant women from Foshan region, Guangdong province

目的对广东佛山地区19297名孕妇进行脊髓性肌萎缩症(SMA)突变的携带者筛查,探讨佛山地区人群运动神经元生存基因1(SMN1)突变的情况。方法采用实时荧光定量PCR技术对19297名孕妇进行SMN1基因第7和第8外显子(E7、E8)缺失检测,对结果为阳性的孕妇配偶进行基因缺失检测,为双方同为携带者的夫妇进行产前SMN1基因分析,并采用多重连接探针扩增技术(MLPA)对胎儿基因结果进行验证。结果在19297例孕妇中,共检出SMA携带者286例(SMN1基因E7、E8杂合缺失258例,单纯E7杂合缺失28例),携带者频率为1.48%。检出双方同为SMA携带者的夫妇6对,经产前诊断基因分析,最终检出SMN1基因E7、E8纯合缺失胎儿1例,SMN1基因E7、E8杂合缺失胎儿4例,正常基因型胎儿1例,与MLPA复核结果一致。结论阐明广东佛山地区SMA突变的携带频率可为遗传咨询和产前诊断提供依据,并对高风险胎儿进行介入性产前基因诊断,可有效预防SMA患儿的出生,对出生缺陷防控具有重要意义。

Objective To analyze the survival motor neuron 1(SMN1) gene mutation in Foshan region, Guangdong,the carriers of spinal muscular atrophy(SMA) mutations among 19297 pregnant women were screened. Methods Real-time quantitative PCR technique was used to detect the deletion of exon 7 and exon 8(E7, E8) of SMN1 gene in 19297 pregnant women. The husbands of pregnant women carrier were also screened, and prenatal genetic analysis was provided for the couples with both positive results. The results were further confirmed by multiplex ligation-dependent probe amplification(MLPA). Results Among the 19297 pregnant women, a total of 286 cases of SMA carriers were found, and the carrier rate was 1.48%. Among which, 258 cases were heterozygous deletion of exon 7 and exon 8(E7, E8) of SMN1 gene, and 28 cases were heterozygous deletion of E7 of SMN1 gene. 6 pairs of couples both as SMA carriers underwent prenatal genetic analysis.Among them, 1 fetus with homozygous deletion of SMN1 E7 and E8, 4 fetuses with heterozygous deletion of SMN1 E7 and E8,and 1 fetus with normal genotype. These results were consistent with the diagnosis by MLPA. Conclusion Determining the frequency of SMA mutation carriers in Foshan region, Guangdong, can provide a theoretical basis for genetic counseling and prenatal diagnosis. The following prenatal genetic analysis for high-risk fetus can effectively prevent the birth of SMA fetus.