Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter
Version of Record online: 27 DEC 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 51, Issue 2, pages 264–270, February 2002
How to Cite
van der Knaap, M. S., Leegwater, P. A. J., Könst, A. A.M., Visser, A., Naidu, S., Oudejans, C. B.M., Schutgens, R. B.H. and Pronk, J. C. (2002), Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol., 51: 264–270. doi: 10.1002/ana.10112
- Issue online: 31 JAN 2002
- Version of Record online: 27 DEC 2001
- Manuscript Accepted: 14 NOV 2001
- Manuscript Received: 30 OCT 2001
- Dutch Organisation for Scientific Research, NWO. Grant Number: 903-42-097
- Dr. W.M. Phelps Foundation. Grant Number: 00026WO
Leukoencephalopathy with vanishing white matter is a recently defined autosomal recessive disorder. The course is chronic progressive with additional episodes of rapid deterioration, provoked by fever and minor head trauma. A previous study showed that mutations in the genes encoding the ε- or the β-subunit of the eukaryotic translation initiation factor eIF2B, a complex consisting of five subunits, cause the disease in most patients. Seven unsolved patients remained. The unsolved patients were investigated by mutation analysis of the genes encoding the α-, γ-, and δ-subunit of eIF2B and the gene encoding the α-subunit of eIF2, because phosphorylation of this latter subunit regulates eIF2B activity. Mutations were found in the genes encoding the α- (1 patient), γ- (2 patients), and δ-subunits (2 patients) of eIF2B, but no mutations were found in the gene encoding the α-subunit of eIF2. In 2, both less typical patients, no mutations were found. Mutations in all five genes 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 circumstances of stress, such as fever. A defect in eIF2B may explain the sensitivity to stress factors in vanishing white matter patients.