目的:探讨3-甲基戊烯二酸尿症(MGA)Ⅰ型患儿的致病变异。方法:回顾性分析。采用高通量测序结合Sanger测序验证对2017年6月盐城市妇幼保健院收治1例Ⅰ型MGA患儿家系进行基因检测，运用生物信息学方法对新变异的致病性进行预测，并对新剪切变异的可能影响进行实验验证。结果:血串联质谱、尿气相色谱质谱结果提示患儿为Ⅰ型MGA。患儿n AUH基因检出复合杂合变异c.373C>T(p.R125W)和c.942+3A>G，分别来自母亲和父亲；3种软件预测错义变异c.373C>T (p.R125W)具有致病性，R125在各物种中高度保守；4种在线分析工具预测新变异c.942+3A>G不影响剪切，但反转录-PCR联合Sanger测序分析表明，该变异引起n AUH基因转录产物第9外显子缺失。患儿出生45 d起予左卡尼汀及无亮氨酸奶粉治疗，体格智力发育正常。n 结论:若患儿临床诊断明确，针对临床意义不明变异需进行RNA分析，验证其对剪切的影响；本研究丰富了n AUH基因的突变谱。n “,”Objective:To investigate the pathogenic variations of a case of 3-methylpenteneduric aciduria (MGA) type Ⅰ.Methods:Retrospective analysis gene variations of the case with MGA type Ⅰ and family members in June 2017 at Yancheng Maternal and Child Health Hospital were detected using high-throughput sequencing combined with Sanger sequencing.The pathogenicity of the novel variations was predicted using the bioinformatic method.The impact of the novel splicing variation was examined through laboratory experiments.Results:Tandem mass spectrometry and gas chromatography-mass spectrometry results diagnosed the case as MGA type Ⅰ.The compound hete-rozygous variations c. 373C>T (p.R125W) and c. 942+ 3A>G of then AUH gene were detected in the patient, which were inherited from the mother and the father, respectively.Bioinformatics analysis indicated that the c. 373C>T(p.R125W) of then AUH gene was pathogenic (3 softwares) and the R125 residue was highly conserved.Reverse transcription-PCR and Sanger sequencing analysis showed that the variation c. 942+ 3A>G caused the deletion ofn AUH gene exon 9, which was failed to be predicted in the 4 types of software.The patient was treated with Levocarnitine and leucine-free milk powder from 45 days after birth.The physical and mental development was normal.n Conclusions:Splicing analysis of blood RNA should be considered for variants of uncertain significance in genetic diseases when the clinical diagnosis is clear.This study enriches the variation spectrum of the n AUH gene.n