Eukaryotic Translation Initiation Factor 2B, Subunit 1

Alternative Names

  • EIF2B1
  • Eukaryotic Translation Initiation Factor 2B, Alpha
  • EIF2B-Alpha
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OMIM Number

606686

Gene Map Locus
12q24.31

Description

The EIF2B1 gene encodes the alpha subunit of the eukaryotic translation initiation factor (EIF2B) protein.  EIF2B is a heterodecameric protein that consists of alpha, beta and delta subunits in the regulatory subcomplex, and gamma and epsilon subunits in the catalytic subcomplex.  The protein functions as a GTP exchange factor for the substrate eIF2.  As GTP-bound eIF2 is responsible for loading the initiator methionyl-tRNA onto the ribosome, EIF2B is essential for the initiation of protein synthesis.  Recent studies have suggested that EIF2B is involved in oligodendrocyte development and the cellular response to stimulus, heat and glucose.

Mutations in this gene are associated with Leukoencephalopathy with Vanishing White Matter (VWM), a neurological disorder characterized by progressive cerebellar ataxia, spasticity, cognitive impairment and variable optic atrophy.

Molecular Genetics

The EIF2B1 gene is located on the long arm of chromosome 12 at position 12q24.31.  It spans a length of 13 kb of DNA and its coding sequence is spread across 9 exons.  The protein product encoded by this gene is made up of 305 amino acids and has a molecular mass of 33.7 kDa.  Alternative splicing results in an additional isoform of this protein comprised of 222 amino acids.  Both homozygous and compound heterozygous mutations in the EIF2B1 gene have been associated with VWM.  These are mainly missense mutations that affect EIF2B GEF activity or the binding of the EIF2B1 subunit to the complex.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Alamri et al. (2016) described the first case of Diabetic Ketoacidosis (DKA) associated with Vanishing White Matter (VWM) disease.  The proband was diagnosed with DKA at 8 months of age and treated with insulin injections.  He was admitted again at 1 year of age due to intractable seizures and convulsions.  Brain CT and MRI helped diagnose him with diffuse white matter disease.  He died at two years of age due to severe hypotonia, gastroesophageal reflux and recurrent chest infections.  His parents were first cousins and they had an unaffected daughter.  They also had two other sons who died at 1 year of age with white matter disease, spastic quadriplegia and insulin dependent diabetes mellitus.  Whole exome sequencing found a homozygous variant in the EIF2B1 gene of the proband (c.146T>G, p.Leu49Arg).  The parents and sister were heterozygous for the mutation.  The variant, which was absent from exome sequencing databases occurred at a highly conserved residue and in-silico analysis predicted it to be pathogenic. 

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