Identification of MRI1, encoding translation initiation factor eIF-2B subunit alpha/beta/delta-like protein, as a candidate locus for infantile epilepsy with severe cystic degeneration of the brain

Gene. 2013 Jan 10;512(2):450-2. doi: 10.1016/j.gene.2012.10.063. Epub 2012 Nov 2.

Abstract

Several neurodegenerative disorders are known to predominantly affect the white matter of the brain including vanishing white matter disease (VWMD), an autosomal recessive disorder characterized by leukodystrophy of varying severity in addition to variable systemic involvement. We report a consanguineous Arab family with three affected children, all of whom presented with severe neonatal epilepsy and profound neurodegenerative disease characterized by marked leukodystrophy with white matter cavitation mimicking VWMD. We combined autozygome and exome analysis to identify a novel variant in the gene encoding a member of the eIF2B-related family of proteins (MRI1). This is a poorly understood family of proteins of unclear function. Our results represent the first link between a variant in a member of this family and a human disease, and suggest that it converges with the highly homologous eIF2B, known to be mutated in VWMD, on the molecular pathogenesis of neurodegeneration.

MeSH terms

  • Adult
  • Aldose-Ketose Isomerases / genetics*
  • Aldose-Ketose Isomerases / metabolism
  • Arabs
  • Epilepsies, Myoclonic / diagnostic imaging
  • Epilepsies, Myoclonic / enzymology
  • Epilepsies, Myoclonic / genetics*
  • Female
  • Genetic Loci*
  • Heredodegenerative Disorders, Nervous System / diagnostic imaging
  • Heredodegenerative Disorders, Nervous System / enzymology
  • Heredodegenerative Disorders, Nervous System / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / enzymology
  • Leukoencephalopathies / genetics*
  • Male
  • Radiography

Substances

  • Aldose-Ketose Isomerases