摘要
目的通过运动神经元存活基因1(SMN1)筛查获得山西省太原地区部分人群的脊髓性肌萎缩症(SMA)携带者频率,并进行SMA阳性家系分析,探讨SMA产前诊断分析的临床价值。方法收集2020年1月至2021年4月在我院就诊的孕妇,共910例,应用实时荧光定量PCR技术对其进行SMN1基因检测和诊断。应用多重连接依赖探针扩增技术(MLPA)对明确有SMA的患者进行家系验证,并对高风险胎儿进行产前诊断,以减少SMA患儿的出生。结果在910例孕妇中发现20例孕妇SMN1基因拷贝数为单拷贝,为SMA携带者(携带率1/46)。进一步对SMA携带者孕妇的配偶进行检测,丈夫同为SMA携带者有3例(2例无先证者,1例有先证者),其中1对夫妇不配合后续检测,对另外2例高风险胎儿进行产前诊断,最终提示1例胎儿SMN1基因7、8外显子杂合缺失;另1例SMN1基因7、8号外显子杂合缺失,SMN2基因7、8号外显子杂合重复。对具有SMA阳性家族史家系验证发现:先证者为SMN1基因第7和第8外显子纯合缺失,SMN2基因7、8号外显子重复变异;先证者父亲和二胎胎儿均为SMN1基因第7和第8外显子杂合缺失,SMN2基因7、8号外显子重复变异;先证者母亲为SMN1基因第7和第8外显子杂合缺失,未发现SMN2基因7、8号外显子存在变异。结论SMN1基因实时荧光定量PCR检测可以区分大部分正常人和SMA携带者,太原地区部分人群中SMA携带频率为21.98‰。应用实时荧光定量PCR检测结合MLPA对于SMA患者进行家系验证,并对高风险胎儿进行产前诊断,对减少SMA患儿的出生具有重要价值。
Objective:To obtain the incidence of carrier of spinal muscular atrophy(SMA)in 910 pregnant woman in Taiyuan,Shanxi Province through screening survival motor neuron gene 1(SMN1),and analyze the positive SMA families to explore the clinical value of prenatal diagnosis and analysis of SMA.Methods:A total of 910 pregnant women treated in our hospital from January 2020 to April 2021 were collected.Real-time fluorescent quantitative PCR technology was used to detect and diagnose the SMN1 gene.The multiple ligation dependent probe amplification technology(MLPA)was used to verify the family of patients with SMA,and prenatal diagnosis of high-risk fetuses was performed to reduce the birth of children with SMA.Results:Among 910 pregnant women,20 pregnant women were found to have a single copy of SMN1 gene,which were SMA carriers(carrying rate 1/46).Further,the spouses of pregnant women with SMA carriers were tested.There were three husbands who were SMA carriers(two without a proband and one with a proband),and the prenatal diagnosis was performed for two high-risk fetuses,one couple did not cooperate with fetal MLPA testing.Finally,one case had a heterozygous deletion in exons 7 and 8 of fetal SMN1 gene.Another case had a heterozygous deletion in exons 7 and 8 of SMN1 gene and heterozygous duplication in exons 7 and 8 of SMN2 gene.The verification of families with SMA positive family history found that the proband had a homozygous deletions in exons 7 and 8 of SMN1 gene,and heterozygous duplication in exons 7 and 8 of SMN2 gene.The father and second fetus of the proband had heterozygous deletion in exons 7 and 8 of SMN1 gene and heterozygous duplication in exons 7 and 8 of SMN2 gene.The mother had heterozygous deletion in exons 7 and 8 of SMN1 gene,and no variation was found in exons 7 and 8 of SMN2 gene.Conclusions:The frequency of SMA carriers in 910 pregnant women in Taiyuan area is 21.98‰.Real time fluorescence quantitative PCR combined with MLPA for family verification of SMA patients and prenatal diagnosis of high-risk fetuses have important value in reducing the birth of SMA children.
作者
邓洋
郭进升
张眉花
DENG Yang;GUO Jin-sheng;ZHANG Mei-hua(Department of Gynecology,Taiyuan Maternal and Child Health Hospital,Taiyuan 030012)
出处
《生殖医学杂志》
CAS
2022年第2期197-201,共5页
Journal of Reproductive Medicine
基金
吴阶平医学基金会临床科研专项资助基金(320.6750.18087)。
关键词
脊髓性肌萎缩症
携带者
SMN1
实时荧光定量PCR
多重连接依赖探针扩增技术
Spinal muscular atrophy(SMA)
Carrier
SMN1
Real-time fluorescent quantitative PCR
Multiple ligation dependent probe amplification technology
