604例育龄期夫妇单基因遗传病携带者筛查的结果分析  

Analysis of the results of screening for carriers of monogenic genetic diseases in 604 couples of childbearing age

作　　者：李倩贇 吴仁花 张媛媛[1,2] 刘芳 程维晟[1,2] 袁静 Li Qianyun;Wu Renhua;Zhang Yuanyuan;Liu Fang;Cheng Weisheng;Yuan Jing(Prenatal Testing Center,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Key Laboratory of Gamete and Reproductive Tract Abnormalities,National Health Commission,Hefei 230022;Dept of Clinical Laboratories,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院产前诊断中心,合肥230022 [2]国家卫生健康委配子及生殖道异常研究重点实验室,合肥230022 [3]安徽医科大学第一附属医院检验科,合肥230022

出　　处：《安徽医科大学学报》2024年第9期1653-1658,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家重点研发计划(编号:2021YFC1005303);国家自然科学基金(编号:82101954);安徽省高校科研项目(编号:2022AH051161);安徽省博士后研究人员科研活动经费资助项目(编号:2022A574)。

摘　　要：目的了解安徽省育龄期人群单基因遗传病致病基因携带情况以及常见变异,探索建立安徽省携带者筛查临床应用网络与转诊模式,探讨在临床实施扩展性携带者筛查(ECS)的应用价值。方法收集备孕或早孕期(≤13+6周)表型正常无遗传病家族史的604例育龄人群样本。采用基于高通量测序结合特殊PCR分析技术,检测与220种疾病相关的致病变异,对阳性携带者的配偶进行相关基因检测。结果截至2023年5月16日,收集到受检样本604例,检测出目标疾病携带者340例;检出致病变异检测阳性率为56.29%;共检出致病变异499个,每名受检者携带0~5个变异;携带1种单基因隐性遗传病致病变异216例,占35.76%,最为常见。携带2种单基因隐性遗传病致病变异95例,占15.73%。截至目前已发报告夫妻302对,筛查中共发现高风险夫妇7对,高风险率为2.32%。遗传模式为常染色体隐性的共5对(夫妻双方均携带同一致病基因),遗传模式为X-连锁的共2对(女方携带X-连锁致病基因)。结论本研究获得了604例接受ECS检测的受检者目标疾病的总体携带和临床应用情况以及常见单基因遗传病致病基因的携带率,可以为安徽省携带者筛查临床应用网络与转诊模式的建立提供科学指导。Objective To understand the carrying situation and common variation of pathogenic genes of single gene hereditary disease in childbearing age population in Anhui province,to explore the establishment of clinical application network and referral model of carrier screening in Anhui province,and to explore the application value of expansible carrier screening(expanded carrier screening,ECS)in clinic.Methods Samples were collected from 604 individuals of childbearing age,all exhibiting a normal phenotype and a family history of inherited disease.These samples were obtained during the first trimester or early stages of pregnancy(≤13+6 weeks).Based on high-throughput sequencing and special PCR analysis techniques,pathogenic variants associated with 220 diseases were detected,and related genes were detected in the spouses of positive carriers.Results As of May 16,2023,604 tested samples had been collected,and 340 carriers of the target disease had been detected;The positive rate of pathogenic variation detection was 56.29%;A total of 499 pathogenic variants were detected,with each tested individual carrying 0-5 variants;216 cases,accounting for 35.76%,carried a single gene recessive disease pathogenic variation,which was the most common.There were 95 cases carrying two types of single gene recessive genetic disease pathogenic variation,accounting for 15.73%.As of now,302 couples have been reported,and a total of 7 high-risk couples have been found through screening,with a high-risk rate of 2.32%.There are a total of 5 pairs with autosomal recessive genetic pattern(both spouses carry the same pathogenic gene),and 2 pairs with X-linked genetic pattern(the female carries the X-linked pathogenic gene).Conclusion In this study,we obtained the overall carrier and clinical application of target diseases as well as the carrier rates of causative genes of common single-gene genetic diseases in 604 subjects who underwent ECS testing,which could provide scientific guidance for the establishment of a clinical application network

关 键 词：单基因遗传病 扩展性携带者筛查 高通量测序 遗传咨询 出生缺陷 产前诊断 二代测序技术 

分 类 号：R715.5[医药卫生—妇产科学]