A novel variation in the Twinkle linker region causing late-onset dementia

Neurogenetics. 2010 Feb;11(1):21-5. doi: 10.1007/s10048-009-0202-4. Epub 2009 Jun 10.

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.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • DNA Helicases / genetics*
  • DNA, Mitochondrial / genetics*
  • Dementia / diagnosis
  • Dementia / genetics*
  • Female
  • Genes, Dominant
  • Humans
  • Male
  • Mitochondrial Diseases / genetics
  • Mitochondrial Proteins
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics
  • Neurophysiology / methods
  • Ophthalmoplegia, Chronic Progressive External / diagnosis
  • Ophthalmoplegia, Chronic Progressive External / genetics*
  • Pedigree

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • DNA Helicases
  • C10ORF2 protein, human