TY - JOUR
T1 - Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter
AU - Van Der Knaap, Marjo S.
AU - Leegwater, Peter A.J.
AU - Könst, Andrea A.M.
AU - Visser, Allerdien
AU - Naidu, Sakkubai
AU - Oudejans, Cees B.M.
AU - Schutgens, Ruud B.H.
AU - Pronk, Jan C.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Brain Diseases/genetics
KW - DNA Mutational Analysis
KW - Eukaryotic Initiation Factor-2B/genetics
KW - Humans
KW - Magnetic Resonance Imaging
KW - Mutation
KW - Nerve Fibers, Myelinated/pathology
KW - Phenotype
KW - Protein Biosynthesis
UR - http://www.scopus.com/inward/record.url?scp=0036156978&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.10112
DO - https://doi.org/10.1002/ana.10112
M3 - Article
C2 - 11835386
SN - 0364-5134
VL - 51
SP - 264
EP - 270
JO - Annals of neurology
JF - Annals of neurology
IS - 2
ER -