甘肃地区新生儿遗传代谢病疾病谱与基因变异分析

Disease Spectrum and Gene Variation Analysis of Neonatal Inherited Metabolic Diseases in Gansu Region

目的:回顾性分析甘肃地区新生儿遗传代谢病的疾病谱、发病率和基因变异谱,探究本地区新生儿遗传代谢病的遗传特征。方法:选择2021年1月—2023年12月在甘肃省妇幼保健院进行遗传代谢病串联质谱筛查的213786例新生儿干血斑样本,可疑阳性患儿进行尿气相质谱和(或)高通量基因测序诊断,对确诊患儿的疾病谱、发病率和基因变异谱进行分析。结果:在189例复筛阳性患儿中确诊145例,包含15种遗传代谢病,甘肃地区遗传代谢病总体发病率为1/1474,其中高苯丙氨酸血症99例,占68.28%,是甘肃地区遗传代谢病中发病率最高的疾病;发现20种变异基因相关的268个变异位点,如一些热点变异:PAH基因c.728G>A、c.611A>G和MMACHC基因c.609G>A、c.567dupT,以及未报道的新变异:MMACHC基因c.298G>T、MUT基因c.2000A>G、MMAA基因c.734-7A>G。结论:质谱学筛查联合基因检测技术可有效探究遗传代谢病的遗传特征,为该类疾病后续的临床诊断及遗传咨询提供数据支撑。

Objective:To retrospectively analyze the disease spectrum,incidence rate and gene variation spectrum of neonatal inherited metabolic diseases in Gansu province,and to explore the genetic characteristics of these diseases.Methods:213786 cases with the dried blood spots were screened by tandem mass spectrometry from January 2021 to December 2023.The suspected positive children were diagnosed by urine gas chromatography mass spectrometry or(and)high-throughput gene sequencing.The spectrum of disease,incidence and gene variation were analyzed.Results:145 cases were diagnosed in 189 high risk newborns,including 15 kinds of inherited metabolic diseases.The total incidence of inherited metabolic diseases in Gansu was 1/1474,among which 68.28%(99 cases)were hyperphenylalanine.A total of 268 mutation sites related to 20 mutation genes were found,such as some hot spot mutations:c.728G>A,c.611A>G mutations in PAH gene,c.609G>A,c.567dupT mutations in MMACHC gene,and the new variants not reported:c.298G>T mutation in MMACHC gene,c.2000A>G mutation in MUT gene,c.734-7A>G mutation in MMAA gene.Conclusions:Mass spectrometry combined with gene detection can effectively explore the genetic characteristics of inherited metabolic diseases,which provides data support for follow-up clinical diagnosis and genetic counseling of these diseases.