Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), an activator of translation initiation factor eIF2.
To the best of our knowledge, this is the first female patient with adult-onset VWMD suffering from long-term menometrorrhagia attributed to the c.254 T > A and c.496A > G mutations in the EIF2B2 gene; the c.496A > G mutation has not been reported in previous studies.
Vanishing white matter disease (VWM) is an inherited leukoencephalopathy in children attributed to mutations in EIF2B1-5, encoding five subunits of eukaryotic translation initiation factor 2B (eIF2B).
Mutations in eIF2B genes cause vanishing white matter disease (VWMD), a fatal leukodystrophy that can manifest following physical trauma or illness, conditions that activate the integrated stress response (ISR).
To examine these issues, we assessed eIF2B body, stress granule, and P-body induction in wild-type yeast cells and cells carrying VWMD alleles in the EIF2B2 (GCD7) and EIF2B5 (GCD6) subunits of eIF2B.
Mutations in the genes encoding eIF2B subunits inhibit the nucleotide exchange and eventually slow down the process of translation, causing vanishing white matter disease.
Vanishing white matter disease (VWM)/childhood ataxia with central hypomyelination (CACH) is an autosomal recessive leukoencephalopathy caused by mutations in one of five genes, EIF2B1-5, encoding the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B).
Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis.
In 283, genetic mutation of EIF2B was confirmed with the onset of vanishing white matter disease reported as antenatal (seven), infantile (eight), early childhood (107), between infantile and early childhood (20), late childhood (25), between early and late childhood (three), adult (68), and between late childhood and adult (21).
We report the clinical description of an Italian patient with c.638A>G mutation in exon 5 of EIF2B2 gene and a very slow progressive Vanishing White Matter disease phenotype.
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.
This complicated the diagnostic workup until homozygosity scan revealed a novel mutation in EIF2B2.This report widens the clinical spectrum of VWMD and raises the possibility of an allele-specific association with adrenal insufficiency.
Functional analysis of recently identified mutations in eukaryotic translation initiation factor 2Bɛ (eIF2Bɛ) identified in Chinese patients with vanishing white matter disease.
Eukaryotic initiation factor 2B (eIF2B)-related disorders are heritable white matter disorders with a variable clinical phenotype (including vanishing white matter disease and ovarioleukodystrophy) and an equally heterogeneous genotype.
Mutations in eukaryotic translation initiation factor 2B (eIF2B) cause Childhood Ataxia with CNS Hypomyelination (CACH), also known as Vanishing White Matter disease (VWM).
Vanishing white matter disease (VWM; MIM #603896), also known as childhood ataxia with central nervous system hypomyelination (CACH) syndrome, is an autosomal recessive transmitted leukoencephalopathy related to mutations in each of the 5 genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5) encoding for the 5 subunits of eukaryotic translation initiation factor 2B (eIF2B), essential for protein synthesis.
Mutations in eukaryotic initiation factor 2B (eIF2B) cause one of the most common leukodystrophies, childhood ataxia with CNS hypomyelination/vanishing white matter disease or CACH/VWM.