4568例孕妇脊髓性肌萎缩症携带者筛查及产前诊断分析  

Screening and Prenatal Diagnosis of 4568 Pregnant Women with Spinal Muscular Atrophy

作　　者：孟雁欣 孙东兰[1] 于湄[1] 杨玉秀[1] 刘春苗 MENG Yanxin;SUN Donglan;YU Mei(Prenatal Diagnosis Center,The Fourth Hospital of Shijiazhuang,Shijiazhuang Hebei 050010,China)

机构地区：[1]石家庄市第四医院产前诊断中心,河北石家庄050010 [2]石家庄市第四医院产一科,河北石家庄050010

出　　处：《实用妇产科杂志》2021年第7期531-535,共5页Journal of Practical Obstetrics and Gynecology

基　　金：河北省青年自然科学基金(编号:H2017106030)。

摘　　要：目的:对4568例孕妇进行脊髓性肌萎缩症(SMA)突变携带者筛查,并对已明确携带者夫妇胎儿进行产前诊断,了解运动神经元生存基因(SMN)变异携带率及SMA产前诊断并分析临床意义。方法:将变性高效液相色谱(DHPLC)分析法及Sanger测序联合应用,对石家庄市第四医院4568例孕妇进行SMN1缺失/点突变检测,进行携带频率统计;对携带者配偶进行筛查并对双方均为携带者夫妇胎儿进行产前诊断。结果:(1)4568例孕妇共检出SMA患者3例,2例SMN1外显子7纯合缺失,1例患者检测出SMN1外显子杂合缺失,拷贝数"1",该患者同时检出SMN1点突变变异位点p.Q164X,临床诊断为"1+1型"SMA患者,发病率0.066%。(2)126例拷贝数异常携带者(SMN1杂合缺失/转换个体),84例为缺失携带者,含SMN1∶SMN 2=1∶1样本35例,SMN1∶SMN 2=1∶2样本49例。35例转换携带者SMN1转换成SM N 2基因,含SMN1∶SMN 2=1∶3样本32例,SMN1∶SMN 2=1∶4样本3例。7例携带者SMN1∶SMN 2=1∶0。(3)126例携带者配偶中25例同为携带者。(4)应用DHPLC联合Sanger测序技术对25例SMA高危胎儿行产前诊断。结果显示3例胎儿SMN1外显子7/8纯合缺失(SMA患者);1例胎儿SMN1外显子7/8杂合缺失(SMA携带者)。余胎儿检测未见SMN1拷贝数异常。Sanger测序1例胎儿携带p.Q164X点突变变异位点,余样本未见SMN异常。结论:本研究检出SMN1变异携带率高于中国南方地区报道,且在北方地区属高携带率地区。DHPLC联合Sanger检测技术可以完成SMA携带者筛查及产前诊断,二者联合应用对于优生优育、有效预防SMA胎儿的出生具有重要的临床意义。Objective:A total of 4568 pregnant women province were screened for spinal muscular atrophy(SMA)mutation carriers,and prenatal diagnosis was conducted with those fetuses of couples with confirmed carriers,so as to understand the carrying rate of the mutation of SMN 1 gene in Hebei province and theclinical significance of prenatal diagnosis of SMA.Methods:Denaturing high-performance liquid chromatography(DHPLC)and Sanger sequencing were used to detect deletion/point mutation of SMN 1 in pregnant women and carry frequency statistics were performed.The carriers′spouses were screened and the couples who were both carriers were given prenatal diagnosis.Results:(1)A total of 3 SMA patients were detected in 4568 pregnant women,including 2 with 7/8 homozygous deletion of the exon SMN 1,and 1 with heterozygous deletion with copy number"1",meanwhile,this patient was detectedpoint mutation locus p.Q164x of SMN 1 and clinically diagnosed as a"1+1"SMA patient,with the incidence of 0.066%.(2)126 out of 4568 pregnant women was detected with abnormal copy number(heterozygous deletion/conversion of SMN 1)and 84 patients with deletion,including 35 patients with SMN 1∶SMN 2=1∶1 and 49 patients with SMN 1∶SMN 2=1∶2.35 carriers were converted from SMN 1 to SMN 2,including 32 samples containing SMN 1∶SMN 2=1∶3 and 3 samples containing SMN 1∶SMN 2=1∶4,meanwhile,7 carriers was identified with SMN 1∶SMN 2=1∶0.(3)Among the 126 carriers,25 male spouses were also carriers.(4)Prenatal diagnosis of 25 SMA high-risk fetuses was performed by DHPLC combined with Sanger sequencing.The results showed that 3 fetuses had 7/8 homozygous deletion of exon SMN 1(SMA patients)and a case of fetal SMN 1 exon 7/8 deletion(SMA carrier).No abnormal copy number of SMN 1 was found in the remaining fetuses.Sanger sequencing confirmed 1 fetus carried p.Q164x mutation locus,and no SMN abnormalities were found in the remaining samples.Conclusions:The SMA carrying rate is higher than that in south China,and it is also a high carrying rate area

关 键 词：变性高效液相色谱技术 Sanger测序 脊髓性肌萎缩症 产前诊断 运动神经元生存基因 

分 类 号：R714.5[医药卫生—妇产科学]