21例甲基丙二酸血症患儿的基因变异分析

Genetic analysis of 21 cases of methylmalonic academia

目的对21个甲基丙二酸血症家系进行遗传学分析,明确致病基因及为患者家系进行遗传咨询提供依据。方法应用高通量测序法对甲基丙二酸血症患儿进行基因变异检测及Sanger测序验证。结果21例甲基丙二酸患者共鉴定出MMUT、MMAA和MMUT3个基因29个变异位点;MMUT基因c.323G>A(10%)、c.917C>T(10%)和c.984delC(10%)变异及MMACHC基因c.609G>A(45%),c.80A>G(10%)和c.567dupT(10%)变异较为常见。其中MMUT基因c.2000A>G、MMACHC基因c.298G>T和MMAA基因c.734-7A>G变异是首次报道的新变异位点。结论对甲基丙二酸血症患者进行基因变异检测可以明确其可能的致病原因,为其临床诊断提供依据,新变异的检出丰富了甲基丙二酸血症致病基因的变异谱。

Objective To carry out genetic analysis for 21 patients with methylmalonic acidemia(MMA)and provide genetic counseling for their families.Methods Next generation sequencing(panel)was used to detect the pathogenic variants underlying the disease.Results In total 29 variant sites of MMUT,MMAA,MMUT were identified in the 21 patients,with common variants including c.323G>A(10%),c.917C>T(10%),c.984delC(10%)of MMUT gene,and c.609G>A(45%),c.80A>G(10%),c.567dupT(10%)of MMACHC gene.Among these,c.2000A>G of MMUT,c.298G>T of MMACHC and c.734-7A>G of MMAA gene were unreported previously.Conclusion Genetic testing for MMA patients can clarify the cause of the disease and provide a basis for the clinical diagnosis.Discovery of novel variants has enriched the mutational spectrum of MMA.