Results of carrier screening for Spinal muscular atrophy among 35 145 reproductive-aged individuals from Dongguan region
赵颖 1娄季武 1付有晴 1戴韵诗 1梁巧仪 1孙曼娜 1谭钧铷 1刘彦慧 1梁程红 李岭
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作者信息
1. 东莞市妇幼保健院 东莞市生殖与遗传研究所产前诊断中心，东莞 523112
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摘要
目的 对东莞地区育龄人群进行脊髓性肌萎缩症(SMA)的携带者筛查，探讨本地区人群SMN1基因缺失的携带率。 方法 选取2020年3月至2022年8月在东莞市妇幼保健院接受SMN1基因筛查的表型正常的育龄期男女为研究对象。采用实时荧光定量PCR(qPCR)技术对受试者SMN1基因的第7/8外显子(E7/E8)进行缺失检测，并对夫妻双方均为携带者的家系应用多重连接探针扩增(MLPA)进行产前诊断。 结果 在35 145例筛查者中，SMN1基因第7外显子缺失的携带者635例(E7/E8杂合缺失586例，E7杂合缺失伴E8纯合缺失2例，单纯E7杂合缺失47例)，携带率为1.81%(635/35 145)。男性携带率为1.59%(29/1 821)，女性携带率为1.82%(606/33 324)，2组差异无统计学意义(χ2 ＝ 0.497，P＝0.481)。1例29岁女性为SMN1基因E7/E8纯合缺失，MLPA验证其SMN1基因型为[0∶ 4]。其家系中有3名[0 ∶ 4]基因型成员均未见相关的临床症状。共11对携带者夫妻进行产前诊断，1例[0 ∶ 4]基因型胎儿被终止妊娠。 结论 本研究首次确定了东莞地区SMA的人群携带率并对高风险夫妇提供了产前诊断，其结果可为SMA的遗传咨询、产前诊断提供参考，对SMA的出生缺陷防控具有重要的意义。 Objective To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations. Methods Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA). Results Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous deletion E7 and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ2 = 0.497, P=0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated. Conclusion This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.
Abstract
Objective To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations. Methods Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA). Results Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous deletion E7 and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ2 = 0.497, P=0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated. Conclusion This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.
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