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.