title: Ovarian failure related to eukaryotic initiation factor 2B mutations.
abstract: Ovarian failure (OF) at age <40 years occurs in approximately 1% of all women. Other than karyotype abnormalities, very few genes are known to be associated with this ovarian dysfunction. We studied eight patients who presented with premature OF and white-matter abnormalities on magnetic resonance imaging. Neurological signs may be absent or present after OF. In seven patients, we report for the first time mutations in three of the five EIF2B genes (EIF2B2, -4, and -5) that were recently shown to cause childhood ataxia with central nervous system hypomyelination/vanishing white-matter disease leukodystrophy. The correlation we observed between the age at onset of the neurological deterioration and the severity of OF suggests a common pathophysiological pathway.
authors.affiliation: INSERM Unité Mixte de Recherche 384, Faculté de Médecine, Clermont-Ferrand, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Fogli
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Eléonore
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: Françoise
authors.initials: F
authors.lastname: Bouhour
authors.forename: Pierre
authors.initials: P
authors.lastname: Labauge
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Meaney
authors.forename: Susan
authors.initials: S
authors.lastname: Zeesman
authors.forename: Christine R
authors.initials: CR
authors.lastname: Kaneski
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
mesh_terms: D017668:Age of Onset; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009186:Myelin Sheath / Q000000981:diagnostic imaging / Q000502:physiology; D016649:Primary Ovarian Insufficiency / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D012720:Severity of Illness Index
chemical_list: D015852:Eukaryotic Initiation Factor-2