Carrier screening for 223 monogenic diseases in Chinese population:a multi-center study in 33 104 individuals
10.12122/j.issn.1673-4254.2024.06.01
- VernacularTitle:中国人群33 104例单基因病携带者筛查的多中心研究
- Author:
Wei HOU
1
;
Xiaolin FU
;
Xiaoxiao XIE
;
Chunyan ZHANG
;
Jiaxin BIAN
;
Xiao MAO
;
Juan WEN
;
Chunyu LUO
;
Hua JIN
;
Qian ZHU
;
Qingwei QI
;
Yeqing QIAN
;
Jing YUAN
;
Yanyan ZHAO
;
Ailan YIN
;
Shutie LI
;
Yulin JIANG
;
Manli ZHANG
;
Rui XIAO
;
Yanping LU
Author Information
1. 中国人民解放军医学院,北京 100853
- Keywords:
genetic carrier screening;
monogenic disorders;
genetic counseling
- From:
Journal of Southern Medical University
2024;44(6):1015-1023
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.
