Vanishing white matter disease: a review with focus on its genetics.
Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts of cerebral white matter vanish and are replaced by fluid. Autopsy confirms white matter rarefaction and cystic degeneration. The process of localization and identification of the first two genes related to VWM, EIF2B5 and EIF2B2, was facilitated by two founder effects in the Dutch population. EIF2B5 and EIF2B2 encode the epsilon and beta subunits of translation initiation factor eIF2B. Soon it was shown that mutations in all five eIF2B subunit genes can cause VWM. EIF2B is essential for the initiation of translation of RNA into protein and is involved in regulation of the process, especially under stress conditions, which may explain the sensitivity to stress conditions observed in VWM patients. The pathophysiology of the disease is still poorly understood.
Pronk
Jan C
JC
Department of Human Genetics, VU University Medical Center, Amsterdam, The Netherlands.
van Kollenburg
Barbara
B
Scheper
Gert C
GC
van der Knaap
Marjo S
MS
D001921:Brain / Q000473:pathology*; D015140:Dementia, Vascular / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D009426:Netherlands; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors; C101003:ELF2 protein, human