摘要
目的探讨中国育龄人群中21种遗传代谢病的携带率,为遗传咨询和生育指导提供依据,同时为新生儿遗传代谢病筛查病种的选择提供一定的参考。方法采集897位无关健康个体(包括143对夫妇)的外周血,提取DNA。应用全外显子组测序技术对该897位个体的54个基因(21种遗传代谢病的致病基因)进行检测,筛选在数据库记载的致病性/疑似致病性变异和未记载的功能丧失型变异。结果897位个体中检出数据库记载的54个致病基因中致病性/疑似致病性变异和未记载的功能丧失型变异共140个,总频次为183次,人均携带0.20个。一对夫妇同时携带SLC25A13基因致病性变异,通过胚胎植入前遗传学诊断生育一健康婴儿。检出的变异涉及40个基因,变异数频次较多的5个基因分别是ATP7B、SLC25A13、PAH、CBS和MMACHC。根据Hardy-Weinberg定律,人群中该21种遗传代谢病发病率约为1/1100,发病率较高的5种单基因病是瓜氨酸血症、甲基丙二酸血症、肝豆状核变性、糖原累积病和苯丙酮尿症。结论本研究初步明确了21种遗传代谢性疾病在中国育龄人群中的携带率及发病率,为新生儿遗传代谢病筛查病种的选择提供了参考。孕前遗传病携带者筛查是主动的一级预防措施,是阻断患儿出生的有效方法。
Objective To determine the carrier rate for 21 inherited metabolic diseases among a Chinese population of childbearing age.Methods A total of 897 unrelated healthy individuals(including 143 couples)were recruited,and DNA was extracted from their peripheral blood samples.Whole exome sequencing(WES)was carried out to screen potential variants among 54 genes associated with 21 inherited metabolic diseases.Pathogenic and likely pathogenic variants and unreported loss-of-function variants were analyzed.Results One hundred fourty types of pathogenic/likely pathogenic variants(with an overall number of 183)and unreported loss-of-function variants were detected,which yield a frequency of 0.20 per capita.A husband and wife were both found to carry pathogenic variants of the SLC25A13 gene and have given birth to a healthy baby with the aid of preimplantation genetic diagnosis.The detected variants have involved 40 genes,with the most common ones including ATP7B,SLC25A13,PAH,CBS and MMACHC.Based on the Hardy-Weinberg equilibrium,the incidence of the 21 inherited metabolic diseases in the population was approximately 1/1100,with the five diseases with higher incidence including citrullinemia,methylmalonic acidemia,Wilson disease,glycogen storage disease,and phenylketonuria.Conclusion This study has preliminarily determined the carrier rate and incidence of 21 inherited metabolic diseases among a Chinese population of childbearing age,which has provided valuable information for the design of neonatal screening program for inherited metabolic diseases.Pre-conception carrier screening can provide an important measure for the prevention of transmission of Mendelian disorders in the population.
作者
徐西林
何文斌
王莹
龚斐
卢光琇
林戈
谭跃球
杜娟
Xu Xilin;He Wenbin;Wang Ying;Gong Fei;Lu Guangxiu;Lin Ge;Tan Yueqiu;Du Juan(College of Life Sciences,Hunan Normal University,Changsha,Hunan 410081,China;National Engineering and Research Center of Human Stem Cells,Changsha,Hunan 410013,China;Reproductive and Genetic Hospital of CITIC-Xiangya,Changsha,Hunan 410078,China;Clinical Research Center for Reproduction and Genetics of Hunan Province,Changsha,Hunan 410078,China;Institute of Reproduction and Stem Cell Engineering,Central South University,Changsha,Hunan 410078,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第3期269-275,共7页
Chinese Journal of Medical Genetics
基金
湖南省科技重大专项(2017SK1030)。
关键词
全外显子组测序
孕前携带者筛查
遗传代谢性疾病
基因变异
Whole exome sequencing
Pre-conception genetic testing
Inherited metabolic disease
Genetic variant
