title: A novel variation in the Twinkle linker region causing late-onset dementia.
abstract: Variations in the mitochondrial helicase Twinkle (PEO1) gene are usually associated with autosomal dominant chronic progressive external ophthalmoplegia (PEO). We describe five patients from two unrelated Alsatian families with the new R374W variation in the Twinkle linker region who progressively developed an autosomal dominant multisystem disorder with PEO, hearing loss, myopathy, dysphagia, dysphonia, sensory neuropathy, and late-onset dementia resembling Alzheimer's disease. These observations demonstrate that Twinkle variations in the linker domain alter cerebral function and further implicate disrupted mitochondrial DNA integrity in the pathogenesis of dementia.
authors.affiliation: Département de Neurologie, Hôpital Civil, BP 426, 67091, Strasbourg, France, Echaniz-Laguna@medecine.u-strasbg.fr
authors.forename: Andoni
authors.initials: A
authors.lastname: Echaniz-Laguna
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Chanson
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Wilhelm
authors.forename: François
authors.initials: F
authors.lastname: Sellal
authors.forename: Martine
authors.initials: M
authors.lastname: Mayençon
authors.forename: Michel
authors.initials: M
authors.lastname: Mohr
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mousson de Camaret
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004265:DNA Helicases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003704:Dementia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics; D024101:Mitochondrial Proteins; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics; D009482:Neurophysiology / Q000379:methods; D017246:Ophthalmoplegia, Chronic Progressive External / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human