摘要
目的采用全外显子组测序技术检测216种单基因遗传病在中国健康育龄期人群中的携带情况及高频致病变异。方法选取2013年1月至2023年12月就诊于北京协和医院行全外显子组测序的健康且无血缘关系育龄人群3 097例(包括1 424对夫妇), 对216种单基因遗传疾病(对应220个基因)的基因携带率、累积携带率、高风险夫妇致病变异携带率及变异谱进行回顾性分析。结果 (1)3 097例受检者216种疾病对应的220个基因的检测结果显示, 1 472例检出致病变异, 检出率47.53%(1 472/3 097), 人均携带0.65个致病变异, 高风险检出率为3.93%(56/1 424)。(2)基因携带率≥1%的基因有16个, ≥0.5%的基因有33个, 多数与遗传代谢病相关。携带率较高的基因及其对应的高频突变分别为GJB2基因c.235del, PAH基因c.728G>A, ATP7B基因c.2333G>T, SLC26A4基因c.919-2A>G, GALC基因c.1901T>C, POLG基因c.2890C>T, SLC22A5基因c.1472C>G, USH2A基因c.2802T>G, SLC25A13基因c.852_855del, GAA基因c.761C>T和c.752C>T。结论本研究初步明确了220个基因在中国育龄期人群中的携带率、对应的216种单基因遗传病在高风险夫妇中的发生率及高频突变, 为设计适合中国人群的扩展性携带者筛查项目提供了依据。
Objective:To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening(ECS)panel with 216 diseases(216-ECS panel)within a Chinese population of childbearing age.Methods:Whole-exome sequencing data from a cohort of 3097 unrelated healthy individuals(including 1424 couples)from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed.Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis.The analysis included variant carrier rate,gene carrier rate,cumulative carrier rate,at-risk couple rates,and variant spectrum.Results:(1)Pathogenic variants were identified in 1472(47.53%,1472/3097)individuals,with an average of 0.65 pathogenic variants per individual.The rate of at-risk couples was 3.93%(56/1424).(2)A total of 180 genes were identified,with 16 genes exhibiting a gene carrier rate of≥1%and 33 genes having a rate of≥0.5%,most of which were associated with inherited metabolic diseases.Noteworthy genes with higher gene carrier rates and high-frequency variants included GJB2:c.235del,PAH:c.728G>A,ATP7B:c.2333G>T,SLC26A4:c.919-2A>G,GALC:c.1901T>C,POLG:c.2890C>T,SLC22A5:c.1472C>G,USH2A:c.2802T>G,SLC25A13:c.852_855del,GAA:c.761C>T and c.752C>T.Conclusion:This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population,laying a foundation for the development of ECS programs tailored to the Chinese population.
作者
郝娜
阴凯丽
张晗喆
戚庆炜
周希亚
吕嬿
蒋宇林
Hao Na;Yin Kaili;Zhang Hanzhe;Qi Qingwei;Zhou Xiya;Lyu Yan;Jiang Yulin(Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,National Clinical Research Center for Obstetric and Gynecologic Diseases,Beijing 100730,China)
出处
《中华妇产科杂志》
CAS
CSCD
北大核心
2024年第10期764-770,共7页
Chinese Journal of Obstetrics and Gynecology
基金
中央高水平医院临床科研专项(2022-PUMCH-B-076)。
