济宁地区有机酸血症筛查阳性病例基因突变特征  

Positive cases of organic acidemia were screened in Jining genetic mutational features

作　　者：杨池菊 周成 万秋花 周艳彬 陈西贵 徐鹏 YANG Chiju;ZHOU Cheng;WAN Qiuhua;ZHOU Yanbin;CHEN Xigui;XU Peng(Jining Maternal and Child Health and Family Planning Service Center,Neonatal Disease screening Center,Jining,Shandong 272000,China)

机构地区：[1]济宁市妇幼保健计划生育服务中心新生儿疾病筛查中心,山东济宁272000

出　　处：《中国优生与遗传杂志》2022年第5期885-890,共6页Chinese Journal of Birth Health & Heredity

基　　金：济宁市重点研发计划项目(2020YXNS049)。

摘　　要：目的了解济宁地区有机酸血症的患病率和基因突变规律。方法采集2014年7月14日至2019年12月31日出生的新生儿血样,用串联质谱技术测定血中氨基酸和肉碱水平,筛查有机酸血症,提取筛查阳性新生儿外周血DNA,用核酸质谱和二代测序进行基因突变分析,用Sanger测序验证。结果从608818例新生儿中筛查出有机酸血症146例,共包含7种疾病,以甲基丙二酸血症和3-甲基巴豆酰辅酶A羧化酶缺乏症最常见,分别占70.55%和15.75%。甲基丙二酸血症cblC型病例中检出的MMACHC基因纯合突变占22.37%(17/76),复合杂合突变占73.68%(56/76),杂合突变占3.95%(3/76),常见的突变位点为c.609G>A(p.W203*)、c.482G>A(p.R161Q)、c.658-660del(p.K220del)。甲基丙二酸血症MUT基因复合杂合占92.30%(24/26),杂合占7.69%(2/26),常见的突变位点c.1106G>A(p.R369H)。甲基丙二酸血症cblA型为MMAA基因位点c.742C>T(p.Q248*)的纯合突变。3-甲基巴豆酰辅酶A羧化酶缺乏症MCCC1突变基因占52.17%(12/23),MCCC2突变基因占47.83%(11/23),常见的突变位点为c.639+2T>A和c.1073-6T>A。丙酸血症PCCA基因突变占25.00%(2/8),PCCB基因突变占75.00%(6/8),常见的突变位点为c.838dupC(p.L280Pfs*11)和c.1316A>G(p.Y439C)。异丁酰辅酶A脱氢酶缺乏症中为ACAD8复合杂合突变。β-酮基硫解酶缺乏症、戊二酸血症Ⅰ型和异戊酸血症检出的突变基因分别是ACTA1、GCDH和IVD,均为复合杂合突变。结论本研究初步掌握了本地区有机酸血症的疾病谱及其热点突变基因位点,为有机酸血症的MS/MS筛查推广应用和精准诊断、早期干预提供依据。Objective To understand the prevalence and gene mutation rules of organic acidemia in Jining area.Methods Blood samples were collected from newborns born from 14 July 2014 to 31 December 2019,blood amino acid and carnitine levels were measured by tandem mass spectrometry,screened for organic acidemia,extracted screening positive neonatal peripheral blood DNA,gene mutation analysis by nucleic acid spectrometry and second generation sequencing,and verified by Sanger sequencing.Results 146 organacidaemia were screened from 608818 newborns,with methymalaemia and 3-methylcarboxylase deficiency the most common,with 70.55% and 15.75%,respectively.Homozygous mutations in the MMACHC gene detected in cblC cases were 22.37%(17/76),compound heterozygous mutations 73.68%(56/76),heterozygous mutations 3.95%(3/76),and the common mutation site was c.609G>A(p.W203*),c.482G>A(p.R161Q),c.658-660del(p.K220del).Compound heterozygous for MUT genes was 92.30%(24/26),heterozygous was 7.69%(2/26),and the common mutation site was c.1106G>A(p.R369H).Homozygous mutation of the CblA type of the MMAA gene locus c.742C>T(p.Q248*).MCCC1 mutation genes for 3-methylpataryl CoA carboxylase deficiency were 52.17%(12/23)and 47.83%(11/23),with common mutation sites of c.639+2T>A and c.1073-6T>A.The PCCA gene mutations are 25.00%(2/8),the PCCB gene mutations are 75.00%(6/8),and the common mutation site is c.1316A>G(p.Y439C).A compound heterozygous mutation is ACAD8 in isobutyl-Coenzyme A dehydrogenase deficiency.The mutated genes detected by-ketothiolase deficiency,glutaraemia type I and isovalproaemia were ACTA1,GCDH and IVD,respectively,which were compound heterozygous mutations.Conclusion This study has preliminarily mastered the disease spectrum and its hotspot mutation gene loci in this region,which provides a basis for the promotion and application of M S/MS screening,accurate diagnosis and early intervention of organic acidemia.

关 键 词：有机酸血症 新生儿疾病筛查 串联质谱 基因分析 

分 类 号：R722.1[医药卫生—儿科]