采用PCR结合毛细管电泳法进行适龄孕妇和智力低下男性的脆性X综合征的筛查及相关家系产前诊断  

Carrier screening and prenatal diagnosis of fragile X syndrome inpregnant women with screening indication and males with unexplained mental retardation by using FragilEase^(TM) PCR

作　　者：单珊 张凯华 侯菲[1] 金华[1] Shan Shan;Zhang Kaihua;Hou Fei;Jin Hua(Antenatal Diagnostic Center,Jinan Maternity and Child Care Hospital,Jinan 250001,China;Medical Research Center,Jinan Maternity and Child Care Hospital,Jinan 250001,China)

机构地区：[1]济南市妇幼保健院产前诊断中心,济南250001 [2]济南市妇幼保健院医学研究中心,济南250001

出　　处：《国际遗传学杂志》2023年第5期329-336,共8页International Journal of Genetics

摘　　要：目的通过回顾性分析, 探讨有脆性X综合征(fragile X syndrome, FXS)筛查指征的孕妇和智力低下男性群体中FMR1基因(CGG)n重复序列多态性分布规律, 为FXS突变携带者提供产前诊断和遗传咨询。方法收集具有FXS筛查指征的孕妇(271例)和有智力低下表现的男性(29例)的外周血样本, 采用PCR结合毛细管电泳法检测FMR1基因(CGG)n重复序列的扩增情况, 分析重复序列的重复数分布、FMR1基因突变携带率, 且为FMR1基因突变携带者提供产前诊断和遗传咨询。结果 271例具有FXS筛查指征的孕妇中检测到最大频率CGG重复基因型为30(128例), 占样本X染色体总数比例为23.62%;29例智力低下男性群体检测到最大频率CGG重复基因型为32(5例), 占样本X染色体总数比例为17.24%。在271例具有FXS筛查指征的孕妇中FMR1基因灰区重复的携带率为1.11%(3/271), 前突变携带率为0.37%(1/271), 且该前突变携带者为前突变与全突变嵌合携带者;在29例智力低下男性群体中FMR1基因有2例全突变携带者, 全突变的携带率为6.89%(2/29)。根据受检者FMR1基因突变情况筛查结果, 对3个FMR1基因突变携带者家系随访并追踪, 3个家系均进行了产前诊断, 并接受了相关遗传咨询和生育指导。结论采用PCR结合毛细管电泳法在具有FXS筛查指征的孕妇和智力低下的男性中进行FMR1基因(CGG)n重复筛查, 有助于为该基因突变灰区携带者和前突变携带者进行遗传咨询和产前诊断提供理论依据, 有效减少FXS患儿的出生。Objectives To provide prenatal diagnosis and genetic counseling for women with screening indication of fragile X syndrome(FXS)and their families by screening and summarizing the distribution of(CGG)n repeats number in FMR1 gene among pregnant women with screening indication of FXS and males with unexplained mental retardation.Methods For 271 pregnant women with screening indication of FXS and 29 males with unexplained mental retardation,the(CGG)n repeats of the FMR1 gene were analyzed by FragilEase™PCR.Prenatal diagnosis was provided to carriers of pre-mutation and full-mutations.Results We found that the most frequent(CGG)n repeats allele was 30 repeats(128/542)in pregnant women with screening indication of FXS and 32 repeats(5/29)in males with unexplained mental retardation.Among 271 pregnant samples,3 gray zone repeats carriers and 1 pre-mutation carriers(one mosaic with pre-mutation and full-mutation)were detected,which gave a prevalence of 1.11%and 0.37%,respectively.Among 29 male samples,2 full-mutation carriers were detected(a prevalence of 6.89%).Prenatal diagnosis and genetic counseling were provided for all families involved in this study.Conclusions FRM1 gene testing in women with screening indication of FXS and in males with unexplained mental retardationcan facilitate prenatal diagnosis and reproductive guidance for carriers of gray zone repeats and pre-mutations.Accurate genetic counseling for carriers of pre-mutation would assist reduction of the birth of children with FXS.

关 键 词：脆性X综合征 FMR1基因 (CGG)n重复 产前诊断 

分 类 号：R714.55[医药卫生—妇产科学]