河南省育龄人群中4种常见遗传代谢病孕前携带者筛查

Carrier screening for 4 inherited metabolic diseases in population of childbearing age from Henan Province

目的:探讨河南省育龄人群中4种常见遗传代谢病(高苯丙氨酸血症、肝豆状核变性、甲基丙二酸血症、眼皮肤白化病)携带者筛查的价值。方法:采集2022年7月至12月参加河南省孕前优生健康检查项目的612对(1224人)育龄夫妇的外周血,采用高通量测序技术检测7个基因(PAH、PTPS、MUT、MMACHC、ATP7B、TYR、OCA2)外显子区及剪切区系列变异。结果:致病基因总体携带率为8.74%(107/1224),PAH、PTPS、ATP7B、MMACHC、MUT、TYR及OCA2基因携带率分别为2.53%、0.33%、2.04%、1.72%、0.74%、1.63%和0.16%;河南省北方地区总携带率(3.35%)最高。PAH基因致病变异检出19种,其中c.721C>T携带率(0.41%)最高。PTPS基因致病变异检出2种,携带率均为0.16%。ATP7B基因致病变异检出9种,其中c.2333G>T携带率(0.49%)最高。MMACHC基因致病变异检出10种,其中c.609G>A携带率(0.41%)最高。MUT致病变异检出6种,其中c.1663G>A携带率(0.33%)最高。TYR基因致病变异检出9种,其中c.929_930insC携带率(0.57%)最高。OCA2基因仅检出1种变异,c.1182+1G>A,携带率为0.16%。根据Hardy-Weinberg定律计算,河南省育龄夫妇该4种遗传代谢病总体患病率约为1/2018。结论:初步明确了4种遗传代谢病在河南省育龄人群中的携带率及患病率,为出生缺陷防控的一级预防提供了参考。

Aim:To evaluate the value of carrier screening for 4 inherited metabolic diseases(hyperphenylalaninemia,Wilson disease,methylmalonic acidemia and oculocutaneous albinism)among population of childbearing age in Henan Province.Methods:A total of 1224(612 couples)were recruited from the Henan preconception eugenics health screening program from July to December,2022,the exon region and splicing region of 7 genes(PAH,PTPS,MUT,MMACHC,ATP7B,TYR,OCA2)were tested by high throughput sequencing.Results:The overall carrying rate of the 4 diseases was 8.74%(107/1224),the carrying rates of PAH,PTPS,ATP7B,MMACHC,MUT,TYR and OCA2 were 2.53%,0.33%,2.04%,1.72%,0.74%,1.63%and 0.16%,respectively,and the highest carrying rate(3.35%)was found in northern Henan Province.A total of 19 pathogenic variants of PAH gene were detected,and the top one variant(0.41%)was c.721C>T.Two pathogenic variants of PTPS gene were detected and the carrying rate were 0.16%.The c.2333G>T was carried most frequently(0.49%)among the totally 9 pathogenic variants of ATP7B gene.The c.609G>A was carried most frequently(0.41%)among the totally 10 pathogenic variants of MMACHC gene.The c.1663G>A was carried most frequently(0.33%)among the totally 6 pathogenic variants of MUT gene.The 9 pathogenic variants of TYR gene were detected,and the carrying rate of c.929_930insC was the highest(0.57%).Only one mutation of OCA2 gene was detected,which was c.1182+1G>A(0.16%).According to the Hardy-Weinberg law,the incidence rate of these 4 inherited metabolic diseases among childbearing age population in Henan Province was about 1/2018.Conclusion:The carrying rate and the morbidity rate of 4 inherited metabolic diseases in population of childbearing age in Henan Province is defined,which could provide a reference for the primary prevention of birth defects.