ABSTRACT
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 the 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 the 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 of 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. 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 AUH gene.