孕前和孕早期155种单基因病扩展型携带者筛查的应用研究  

Application study of extended carrier screening of 155 monogenic diseases before and early pregnancy

作　　者：谢晓媛[1] 李阔韬 吴芳[1] 张钰[1] 王蕾棽[1] 刘霞[1] XIE Xiaoyuan;LI Kuotao;WU Fang;ZHANG Yu;Wang Leishen;LIU Xia(Tianjin Women’s&Children’s Health Center,Tianjin 300070,China)

机构地区：[1]天津市妇女儿童保健中心,天津300070

出　　处：《中国优生与遗传杂志》2023年第11期2253-2257,共5页Chinese Journal of Birth Health & Heredity

基　　金：天津市卫生健康委员会科技项目(MS20018);天津市医学重点学科(专科)建设项目资助(TJYXZDXK-075C)。

摘　　要：目的探讨妊娠前和妊娠早期155种单基因疾病携带者筛查(ECS)的临床应用价值。方法回顾性分析2019年12月至2022年6月,在天津市妇女儿童保健中心遗传和优生门诊进行孕前检查和产前检查夫妇的临床资料,总结分析其隐性单基因病携带率、致病基因种类筛选、夫妻双方具有相同基因变异的发生率。结果包括182对夫妇共415人同时接受筛查,统计有6个民族在内,以汉族人群为主(357,86%)。基因变异在入组人群中共携带33.73%,变异基因携带率最高的两个遗传病分别为常染色体隐性遗传耳聋1A型(GJB2基因)携带率为5.30%(22/415)和苯丙酮尿症(PAH基因)携带率为4.58%(19/415)。研究共发现了55种致病突变,前五名的突变基因分别是GJB2、PAH、ATP7B、HBA1/HBA2和MMACHC,检测出4对高危夫妇(2.20%,4/182),经遗传咨询后,其中1对(25%,1/4)选择了胚胎移植前基因病遗传检测(PGT-M)。结论在孕前和孕早期通过单基因疾病携带者筛查可及时发现致病变异携带情况,通过遗传咨询、产前检查或诊断、辅助生殖技术等可有效预防部分单基因遗传病的首次发生。Objective To explore the clinical application of extended carrier screening(ECS)for 155 monogenic diseases during pre-gestational and early pregnancy stages.Methods Clinical data of couples underwent pre-gestational or prenatal examinations in the Genetic and Eugenics Clinic of Tianjin Women’s&Children’s Health Center from December 2019 to June 2022 were retrospectively analyzed by summarizing the population allele frequencies of each recessive monogenic diseases,followed by identification of pathogenic genotypes,and calculating occurrence rate of couples carrying pathogenic mutations on same genes.Results This retrospective cohort consists of 415 individuals(including 182 married couples)from 6 different ethnic groups,with Han group accounting for 86%of the population(357 individuals).Total carrier frequency of all variants reached 33.73%in this cohort,and the two genes with highest carrier rates are GJB2 and PAH,with carrier rates of 5.30%(22/415)and 4.58%(19/415),respectively.A total of 55 genes with pathogenic mutations were found,and the top five genes with highest mutation rates were GJB2,PAH,ATP7B,HBA1/HBA2 and MMACHC.Four high-risk couples(2.20%,4/182)were identified as high-risk cases,and were referred to medical geneticists for systematic genetic counseling.After genetic counseling,one of the high-risk couples(25%,1/4)decided to undergo PGT-M(pre-implantation genetic testing for monogenic disorders)for their upcoming pregnancy.Conclusion ECS at pre-gestational and early pregnancy stage allows for early identification of pathogenic mutations in the future parents,which,in combination with systematic genetic counseling,prenatal tests/diagnosis,and other assisted reproductive techniques,helps to control the occurrence of monogenic diseases.

关 键 词：孕前扩展性单基因病携带者筛查 产前诊断 单基因遗传病 基因突变 

分 类 号：R714.5[医药卫生—妇产科学]