The spacer sequence between the palindromic motifs is constant in length, but its sequence is highly variable among viral species, presenting a relaxed consensus (TT)GGKCCCY, which is similar to the Conserved Late Element or CLE (GTGGTCCC), a putative TrAP-responsive element.
We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12.
Whole-exome sequencing identified two heterozygous mutations in the EIF2B5 gene: a known mutation, c.584G>A (R195H, which is homozygous in CLE), and a novel mutation, c.1223T>C (I408T, which resides in the "I-patch").
Ovarioleukodystrophy: report of a case with the c.338G>A (p.Arg113His) mutation on exon 3 and the c.896G>A (p.Arg299His) mutation on exon 7 of the EIF2B5 gene.
The typical MRI pattern with a diffuse CSF-like aspect of the cerebral white matter can lack particularly in the adult forms whereas an increasing number of patients with clinical and MRI criteria for CACH/VWM disease but without eIF2B mutations are found.
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 linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways.