An unmasked mutation of EIF2B2 due to submicroscopic deletion of 14q24.3 in a patient with vanishing white matter disease

Am J Med Genet A. 2012 Jul;158A(7):1771-7. doi: 10.1002/ajmg.a.35431. Epub 2012 Jun 7.

Abstract

Leukodystrophy with vanishing white matter (VWM) is a neurodegenerative disorder with autosomal recessive traits that is caused by alteration of the eukaryotic translation initiation factor-2B (EIF2B). An 11-month-old patient with distinctive features began to exhibit progressive developmental deterioration associated with intractable epilepsy, which was triggered by recurrent acute infectious diseases. Brain magnetic resonance imaging (MRI) revealed abnormal white matter intensity. Chromosomal microarray testing identified a submicroscopic deletion at 14q24.3 that included EIF2B2, the gene encoding one of the subunits of EIF2B. Because the patient's clinical findings were distinctive for VWM, compound heterozygous mutations of EIF2B2 were suspected, and subsequent sequencing analysis of the remaining allele unmasked the existence of a novel missense mutation of EIF2B2 (V85W). Some distinctive features including small palpebral fissures, bushy eyebrows, ear abnormalities, small upturned nose, downturned corners of the mouth, and micrognathia may be the common features of the patients with 14q24.3 deletions.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 14*
  • Comparative Genomic Hybridization
  • Eukaryotic Initiation Factor-2B / genetics*
  • Facies
  • Genetic Association Studies
  • Humans
  • Leukoencephalopathies / diagnosis
  • Leukoencephalopathies / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Neuroimaging

Substances

  • Eukaryotic Initiation Factor-2B