AUTHOR=Tian Yun , Liu Qiong , Zhou Yafang , Chen Xiao-Yu , Pan Yongcheng , Xu Hongwei , Yang Zhuanyi 

TITLE=Identification of a Novel Heterozygous Mutation in the EIF2B4 Gene Associated With Vanishing White Matter Disease

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.901452

DOI=10.3389/fbioe.2022.901452

ISSN=2296-4185

ABSTRACT=Vanishing white matter disease (VWM) is one of the most common childhood inherited leukoencephalopathy with autosomal recessive inheritance. Mutations in the 5 genes EIF2B1-5 had been identified as the major cause of VWM. In this study, targeted gene capture sequencing panel composed of 160 known pathogenic genes associated with leukoencephalopathies was performed in a large family affected with adult-onset VWM, and a novel heterozygous missense mutation (c.1337G>A: [p. R446H]) in EIF2B4 (NM_001034116.2) was detected. Further functional study in HEK293 cells showed dramatically reduced EIF2B4 protein level in the mutated group compared with the wild-type group. This study revealed a heterozygous missense mutation (c.1337G>A: [p. R446H]) in EIF2B4, which was potentially associated with adult-onset mild phenotype of VWM. Different from previously reported, autosomal dominant inheritance could also be observed in adult-onset VWM.