乌鲁木齐地区育龄女性脊髓性肌萎缩症携带者筛查胚胎植入前诊断及产前诊断情况分析

Carrier screening and pre-implantation genetic diagnosis and prenatal diagnosis for spinal muscular atrophy of pregnant women in Urumqi area

目的 了解乌鲁木齐地区脊髓性肌萎缩症(SMA)的人群携带率,对乌鲁木齐地区孕前女性进行携带者筛查,并召回携带者配偶进行检测,对筛查出的高风险夫妻行单基因病胚胎遗传学检测(PGT-M),对曾生育过SMA患儿的高风险夫妻行产前诊断,为该地区SMA的一级预防和二级预防提供指导。方法 选取2020年1月—2023年7月在新疆医科大学第一附属医院就诊的选择做SMA携带者筛查的育龄期女性7 158例为研究对象,均无SMA表型及相关疾病史。携带者筛查用PCR-熔解曲线法,检测SMN1基因E7、E8的拷贝数,统计乌鲁木齐地区育龄期女性SMA携带者频率;用二代测序的方法对高风险夫妻的胚胎进行PGT-M;对高风险胎儿,用多重连接依赖式探针扩增(MLPA)的方法进行产前诊断。结果 在7 158例育龄期女性中,共检出117例SMA携带者,携带频率为1.63%(1/61);检出双方均为携带者的夫妇1对,而PGT-M技术为这对高风险夫妻选择出未携带突变的整倍体囊胚1枚,携带父源突变单拷贝的整倍体囊胚1枚;产前诊断夫妻的胎儿SMN1基因E7、E8均为2个拷贝数,胎儿出生后随访1年发育未见异常。结论 初步获得乌鲁木齐地区育龄女性SMA携带率为1.63%;对于明确缺失类型和基因型的SMA携带者夫妻,PGT-M技术能够阻断SMA致病基因向后代的传递;对于高风险胎儿,MLPA可给出明确诊断,阻止SMA患儿的出生。该研究有效完成了SMA的一级预防和二级预防,对乌鲁木齐地区出生缺陷防控具有重要意义。

Objective To understand the population carrying rate of spinal muscular atrophy(SMA)in Urumqi,carry out carrier screening among pre-pregnant women in Urumqi,and recall carrier spouses for testing,pre-implantation genetic testing for monogenic disorders(PCT-M)was performed for couples at high risk of screening,prenatal diagnosis was performed for high-risk couples who had previously given birth to children with SMA,and guidance was provided for primary and secondary prevention of SMA in Urumqi.Methods A total of 7158 women of childbearing age who were selected for SMA carrier screening in the First Affiliated Hospital of Xinjiang Medical University from January 2020 to July 2023 were selected as the research objects.Allof them had no history of SMA phenotype or related diseases.The copy number of SMN1 gene E7 and E8 was detected in 7158 women of childbearing age by PCR-melting curve method,and the carrier frequency was calculated;PGT-M of embryos from high-risk couples was performed by second-generation sequencing;and the multiplex ligation-dependent probe amplification(MLPA)method was used for prenatal diagnosis of fetuses in high-risk couples who had previously given birth to children with SMA.ResultsAmong the 7158 women of childbearing age,117 SMA carriers were detected,with the carrying rate of 1.63%(1/61),and a couple with both SMA carriers were detected two euploid blastocysts were finally obtained for the PGT-M needed high-risk couple:one euploid blastocyst without mutation and one euploid blastocyst with single copy of paternal mutation.The fetus of the couple with prenatal diagnosis had 2 copies of exons 7 and 8 of SMNl gene,and no abnormalities were found during the development of the fetus after I year of follow-up.Conclusion The carrying rate of SMA in women of childbearing age in Urumqi was 1.63%.For SMA carrier couples with clear deletion types and genotypes,PGT-M technology can block the transmission of SMA pathogenic genes to their offspring.Prenatal diagnosis for high-risk fetuses can effectively prevent the birth of SMA children.The study effectively completed the primary and secondary prevention of SMA,and has important significance for the prevention and controlof birth defects in Urumqi.