A novel variation in the Twinkle linker region causing late-onset dementia.
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.
Echaniz-Laguna
Andoni
A
Département de Neurologie, Hôpital Civil, BP 426, 67091, Strasbourg, France, Echaniz-Laguna@medecine.u-strasbg.fr
Chanson
Jean-Baptiste
JB
Wilhelm
Jean-Marie
JM
Sellal
François
F
Mayençon
Martine
M
Mohr
Michel
M
Tranchant
Christine
C
Mousson de Camaret
Bénédicte
B
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
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human