Frontiers in Bioengineering and Biotechnology (Jul 2022)

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

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

DOI
https://doi.org/10.3389/fbioe.2022.901452
Journal volume & issue
Vol. 10

Abstract

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Vanishing white matter disease (VWM) is one of the most common childhood inherited leukoencephalopathies with autosomal recessive inheritance. Mutations in five genes, EIF2B1-5, have been identified as the major cause of VWM. In this study, a targeted gene capture sequencing panel comprising 160 known pathogenic genes associated with leukoencephalopathies was performed in a large Han Chinese family affected by adult-onset VWM, and a novel heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 (NM_001034116.2) was detected. Further functional studies in HEK 293 cells showed dramatically reduced EIF2Bδ protein levels in the mutated group compared with the wild-type group. This study revealed that a heterozygous missense mutation (c.1337G > A [p. R446H]) in EIF2B4 was potentially associated with the adult-onset mild phenotype of VWM. In contrast to previous reports, autosomal dominant inheritance was also observed in adult-onset VWM.

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