title: Identification of ten novel mutations in patients with eIF2B-related disorders.
abstract: Autosomal recessive inherited mutations in each of the five eukaryotic initiation factor 2B (eIF2B) subunits are known to cause white matter abnormalities with a wide continuum of clinical signs and severity leading to the concept of eIF2B-related disorders. The clinical spectrum extends from fatal infantile forms to adult forms with slow or absent neurological deterioration. In this study 15 well-characterised patients with the classical form of leukoencephalopathy with vanishing white matter (VWM) or with phenotypic variants like ovarioleukodystrophy were investigated for mutations in the genes EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5 encoding eIF2B. We identified one novel nonsense mutation (EIF2B4, c.625C>T, p.Arg209X), one novel frameshift mutation (EIF2B5, c.453_454del, p.Tyr152fsX12), eight novel missense muations (EIF2B1, c.547G>T, p.Val183Phe; EIF2B2, c. 586C>T, p.Pro196Ser; EIF2B4, c.806T>G, p.Leu269Arg; EIF2B5, c.203T>C, p.Leu68Ser; EIF2B5, c.220G>A, p.Ala74Thr; EIF2B5, c.805C>G, p.Arg269Gly; EIF2B5, c.929G>T, p.Cys310Phe; EIF2B5, c.1003T>C, p.Cys335Arg), and eight previously described alterations.
authors.affiliation: Department of Pediatrics and Pediatric Neurology, Georg August University, Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ohlenbusch
authors.forename: Marco
authors.initials: M
authors.lastname: Henneke
authors.forename: Knut
authors.initials: K
authors.lastname: Brockmann
authors.forename: Maria
authors.initials: M
authors.lastname: Goerg
authors.forename: Folker
authors.initials: F
authors.lastname: Hanefeld
authors.forename: Alfried
authors.initials: A
authors.lastname: Kohlschütter
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001927:Brain Diseases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D020717:Eukaryotic Initiation Factor-2B / Q000235:genetics* / Q000502:physiology*; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D007223:Infant; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D020717:Eukaryotic Initiation Factor-2B