摘要
目的 了解山东省济宁市新生儿尿素循环障碍疾病的发病率、串联质谱(MS/MS)筛查结果和基因突变特征。方法 采集2014年7月至2023年12月出生并参加遗传代谢病筛查的789886名新生儿足跟血样,用MS/MS检测血氨基酸浓度筛查尿素循环障碍疾病,用核酸质谱、二代测序检测突变基因,用Sanger测序验证。结果 从789886名新生儿中,共检出尿素循环障碍患儿40例,总发病率约为0.51/万。共检出6种尿素循环障碍疾病,其中希特林蛋白缺乏症最常见(20/40,50.00%),发病率约0.25/万;其次为瓜氨酸血症Ⅰ型(10/40,25.00%),发病率约0.13/万;鸟氨酸氨甲酰转移酶缺乏症(4/40,10.00%),发病率约0.05/万;精氨酸血症(3/40,7.50%)、氨甲酰磷酸合成酶缺乏症(2/40,5.00%)、精氨酸琥珀酰尿症(1/40,2.50%)少见。希特林蛋白缺乏症、瓜氨酸血症Ⅰ型和精氨酸琥珀酰尿症的MS/MS筛查指标瓜氨酸(Cit)升高伴Cit/苯丙氨酸(Phe)比值升高,鸟氨酸氨甲酰转移酶缺乏症和氨甲酰磷酸合成酶缺乏症的MS/MS筛查指标Cit降低伴Cit/Phe降低,精氨酸血症MS/MS筛查指标精氨酸(Arg)升高伴Arg/鸟氨酸(Orn)和Arg/Phe比值升高。从40例尿素循环障碍患儿中共检出6个突变基因,SLC25A13基因以复合杂合突变为主(15/20,75.00%),常见的突变位点为c.852_855del(p.M285Pfs*2)(17/39,43.59%),其次为c.1177+1G>A(/)(4/39,10.26%);ASS1基因以复合杂合突变为主(9/10,90.00%),突变位点以c.952G>T(p.A318S)和c.953C>T(p.A318V)常见(3/19,15.79%);OTC基因以半合子突变为主(3/4,75.00%),ARG1基因以复合杂合突变为主(2/2,100.00%),CPS1基因以杂合突变为主(2/2,100.00%),ASL基因以复合杂合为主(1/1,100.00%)。5例携带一个突变位点的尿素循环障碍患儿均出现MS/MS筛查主要指标均异常,部分病例辅助检测指标异常或在正常范围。结论 山东省济宁市尿素循环障碍发病率为0.51/万,疾病构成以希特林蛋白缺乏症和瓜氨酸血症Ⅰ型最常见,c.852_85
Objective To understand the incidence rate,tandem mass spectrometry(MS/MS)screening results and gene mutation characteristics of neonatal urea cycle disorders in Jining City,Shandong Province.Methods Blood samples from 789886 newborns born from July 2014 to December 2023 and screened for genetic and metabolic diseases were collected,and the blood amino acid concentration was detected by nucleic acid mass spectrum and second-generation sequencing,and verified by Sanger sequencing.Results Forty children with urea cycle disorder were screened out of 789886 newborns,with an incidence rate of 0.51/10000.Six urea cycle disorders were detected,of which Hitler protein deficiency was the most common(20/40,50.00%),followed by type I(10/40,25.00%of citrullinemia),about 0.13/million;transferase deficiency(4/40,10.00%),aminyl phosphosynthetase deficiency(2/40,5.00%)and arginine succinuria(1/40,2.50%).MS/MS screening index citrullinine(Cit)increased Hetering protein deficiency,citrullinemia type I and arginine succinyluria with increased Cit/phenylalanine(Phe)ratio,MS/MS screening index Cit decreased ornithine carbamidyltransferase deficiency and carbamyl phosphate synthase deficiency with decreased Cit/Phe,argininemia MS/MS screening index arginine(Arg)with increased Arg/Ornithine(Orn)and Arg/Phe ratios.A total of six mutated genes were detected from 40 children with urea cycle disor-der,SLC25A13 Gene is dominated by compound heterozygous mutations(15/20,75.00%).The common mutation site is c.852_855del(p.M285Pfs*2)(17/39,43.59%).Followed by c.1177+1G>A()(4/39,10.26%).The ASS1 gene is dominated by compound heterozygous mutations(9/10,90.00%).Mutation sites are common in c.952G>T(p.A318S)and c.953C>T(p.A318V)(3/19,15.79%).OTC genes are dominated by hemizygous mutations(3/4,75.00%).The ARG1 gene is dominated by compound heterozygous mutations(2/2,100.00%).The CPS1 gene is dominated by heterozygous mutations(2/2,100.00%).The ASL genes were mainly compound heterozygous(1/1,100.00%).All 5 children with urea cycle disorder carrying
作者
孟伟
邵媛媛
杨池菊
陈西贵
徐鹏
周成
MENG Wei;SHAO Yuanyuan;YANG Chiju;CHEN Xigui;XU Peng;ZHOU Cheng(Medical Laboratory,Zoucheng People's Hospital,Zoucheng,Shandong 273500,China;Obstetrics Department,Jining City First People's Hospital,Jining,Shandong 272000,China;Neonatal Disease Screening Center,Jining Maternal and Child Health and Family Planning Service Center,Jining,Shandong 272000,China)
出处
《中国优生与遗传杂志》
2024年第7期1491-1496,共6页
Chinese Journal of Birth Health & Heredity
基金
济宁市重点研发计划项目(2020YXNS049)。
关键词
尿素循环障碍
新生儿疾病筛查
串联质谱
基因分析
urea cycle disorders
neonatal disease screening
tandem mass spectrometry
gene analysis
