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- Title
Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter.
- Authors
Leegwater, Peter A.J.; Vermeulen, Gerre; Könst, Andrea A.M.; Naidu, Sakkubai; Mulders, Joyce; Visser, Allerdien; Kersbergen, Paula; Mobach, Dragosh; Fonds, Dafna; van Berkel, Carola G.M.; Lemmers, Richard J.L.F.; Frants, Rune R.; Oudejans, Cees B.M.; Schutgens, Ruud B.H.; Pronk, Jan C.; van der Knaap, Marjo S.
- Abstract
Leukoencephalopathy with vanishing white matter (VWM) is an inherited brain disease that occurs mainly in children. The course is chronic-progressive with additional episodes of rapid deterioration following febrile infection or minor head trauma. We have identified mutations in EIF2B5 and EIF2B2, encoding the ε- and β-subunits of the translation initiation factor elF2B and located on chromosomes 3q27 and 14q24, respectively, as causing VWM. We found 16 different mutations in EIF2B5 in 29 patients from 23 families. We also found two distantly related individuals who were homozygous with respect to a missense mutation in EIF2B2, affecting a conserved amino acid. Three other patients also had mutations in EIF2B2. As elF2B has an essential role in the regulation of translation under different conditions, including stress, this may explain the rapid deterioration of people with VWM under stress. Mutant translation initiation factors have not previously been implicated in disease.
- Subjects
GENETIC translation; GENETIC mutation
- Publication
Nature Genetics, 2001, Vol 29, Issue 4, p383
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng764