摘要
目的对比分析济南地区甲基丙二酸血症(MMA)生化筛查与基因筛查的发病率及基因变异情况,调查济南地区人群中MMA相关致病基因的携带情况。方法回顾性研究。统计2011年5月至2022年5月山东大学新生儿疾病筛查中心通过串联质谱筛查确诊MMA的患儿,并对基因检测结果进行分析总结。收集6800例新生儿的足跟血滤纸干血斑完成新生儿基因筛查,其中4800例用高通量测序+目标区域捕获技术检测MMAA、MMAB、MMACHC及MMUT基因,2000例采用超多重聚合酶链反应+目标基因位点捕获技术检测MMA相关8个基因174个目标基因位点。分析MMA的热点突变及相关基因携带率。结果共367452名新生儿完成串联质谱筛查,筛查确诊MMA患儿103例(男56例,女47例),MMA生物化学筛查的发病率为1∶3567。其中76例获得基因确诊,检出4种MMA相关基因(MMACHC、MMUT、MMAA、MMADHC)变异。6800例新生儿完成了新生儿基因筛查,共3例患儿确诊MMA,318例患儿携带甲基丙二酸的致病变异,总携带率为4.68%,其中MMACHC基因变异的携带率为3.09%(210/6800),MMUT基因变异的携带率为1.43%(97/6800)。结论MMA为我国最高发的有机酸代谢障碍,济南地区该病发病率及携带率较高,新生儿基因筛查可作为新生儿生化筛查的重要补充,建议本地域育龄夫妇进行MMA相关致病基因的携带者筛查。
Objective To investigate the incidence rate and gene variation of methylmalonic academia(MMA)in Ji′nan city by analyzing biochemical and genetic screening results,and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6800 newborns were tested for neonatal gene screening.MMAA,MMAB,MMACHC and MMUT genes in 4800 cases were detected by high-throughput sequencing+target area capture technology.Ultra-multiplex polymerase chain reaction+target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed.Results A total of 367452 newborns were screened by tandem mass spectrometry,and 103 cases(56 males and 47 females)were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3567.Among the 103 MMA cases,76 were genetically diagnosed,and 4 gene variants of MMA(MMAHC,MMUT,MMAA,MMADHC)were identified.A total of 6800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA,with a total carrier rate of 4.68%.Specifically,the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6800)and 1.43%(97/6800),respectively.Conclusions MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.
作者
李育霖
孙萌
李盼盼
田丽萍
郭元芳
李改杰
李若彤
闫妍
李青
邹卉
Li Yulin;Sun Meng;Li Panpan;Tian Liping;Guo Yuanfang;Li Gaijie;Li Ruotong;Yan Yan;Li Qing;Zou Hui(Department of Neonatal Disease Screening Centre,Ji′nan Maternity and Child Care Hospital Affiliated to Shandong First Medical University,Ji′nan 250001,China)
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2023年第1期54-59,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
山东省自然科学基金(ZR2020MH334)
