These histories expand the prenatal phenotype of eIF2b-related disorders and poignantly illustrate the impact that unbiased genomic sequencing can have on the diagnosis and medical decision making for families affected by childhood neurodegenerative disorders.
Further dissection of the signaling network associated with eIF2B function will help generating therapeutic strategies for VWM disease and possibly other neurodegenerative disorders.
Recessive inherited mutations in any of five subunits of the general protein synthesis factoreIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum.
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).
The importance of correct control of eIF2 and eIF2B for normal physiology is underlined by the recent involvement of the five genes that encode the five eIF2B subunits in a severe autosomal recessive neurodegenerative disease, described in young children as CACH (childhood ataxia with central nervous system hypomyelination)/VWM (leukoencephalopathy with vanishing white matter) syndrome.
Leukoencephalopathy with vanishing white matter (VWM) is a severe inherited human neurodegenerative disorder that is caused by mutations in the genes for the subunits of eukaryotic initiation factor 2B (eIF2B), a heteropentameric guanine nucleotide exchange factor that regulates both global and mRNA-specific translation.
It has been discovered recently that mutations in subunits of eukaryotic initiation factor 2B (eIF2B) underlie the neurodegenerative disease termed 'vanishing white matter'.