强直性肌营养不良症的产前诊断及家系分析  

Prenatal diagnosis and family analysis of myotonic dystrophy

作　　者：傅丹[1] 赵艳[2] 张素华[1] FU Dan;ZHAO Yan;ZHANG Suhua(Department of Prenatal Diagnosis,Subei People's Hospital of Jiangsu Province,Yangzhou,Jiangsu 225001,China;Medical Research Center,Subei People's Hospital of Jiangsu Province,Yangzhou,Jiangsu 225001,China)

机构地区：[1]江苏省苏北人民医院产前诊断中心,江苏扬州225001 [2]江苏省苏北人民医院医学实验研究中心,江苏扬州225001

出　　处：《中国优生与遗传杂志》2024年第5期928-933,共6页Chinese Journal of Birth Health & Heredity

基　　金：江苏省妇幼健康科研项目(F201944);扬州市科技计划项目(YZ2023100)。

摘　　要：目的通过检测强直性肌营养不良(DM)家系中临床疑似DM孕妇及其胎儿的强直性肌营养不良蛋白激酶(DMPK)基因中的CTG三核苷酸重复拷贝数,为DM家族中的患者和疑似个体的基因诊断及产前检查提供科学依据,以证实进行产前诊断的必要性。方法采用全外显子组测序(WES)及线粒体基因组检测、PCR联合毛细管电泳法,检测DM家系中可疑孕妇的外周血,胎儿的羊水及孕妇妹妹外周血中DMPK基因中CTG三核苷酸重复拷贝次数。结果胎儿WES结果未发现复合表型的新发变异或复合杂合突变,在受检者中未检测到明确致病性或疑似致病性拷贝数变异(CNV)。孕妇、胎儿及孕妇妹妹的DMPK等位基因CTG重复次数>100次,属于经典型动态突变。结论具有DM遗传家族病史的孕妇应及时进行产前诊断,以避免DM患儿的出生,提高人口素质。Objective By detecting the CTG trinucleotide repeat copy number in the myotonic dystrophin protein kinase(DMPK)gene in pregnant women with clinically suspected myotonic muscular dystrophy(DM)and her fetus in DM families,we can identify patients and suspected DM patients in DM families.Individual genetic diagnosis and prenatal testing provide scientific basis to confirm the necessity of prenatal diagnosis.Methods We used whole exon sequencing,mitochondrial genome detection,PCR combined with capillary electrophoresis to detect the number of CTG trinucleotide repeat copies in the DMPK gene respectively in peripheral blood of suspected pregnant women in families with myotonic dystrophy,fetal amniotic fluid,and peripheral blood of pregnant women's sisters.Results Fetal WES results did not reveal de novo variants or compound heterozygous mutations for the composite phenotype,also did not detect clear or suspected pathogenic copy number variations(CNVs)in the subjects.The CTG repeat frequency of the DMPK allele in pregnant women,fetuses,and pregnant women's sisters is greater than 100,indicating a classical dynamic mutation.Conclusion Pregnant women with a family history of DM genetics should undergo prenatal diagnosis in time to avoid the birth of children with DM and improve the quality of the population.

关 键 词：强直性肌营养不良症 CTG重复拷贝数 产前诊断 遗传咨询 

分 类 号：R714.5[医药卫生—妇产科学]