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.
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The authors (Andoni Echaniz-Laguna, Jean-Baptiste Chanson, Jean-Marie Wilhelm, François Sellal, Martine Mayençon, Michel Mohr, Christine Tranchant, Bénédicte Mousson de Camaret) disclose all financial support for their work and other potential conflicts of interest.
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Echaniz-Laguna, A., Chanson, JB., Wilhelm, JM. et al. A novel variation in the Twinkle linker region causing late-onset dementia. Neurogenetics 11, 21–25 (2010). https://doi.org/10.1007/s10048-009-0202-4
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DOI: https://doi.org/10.1007/s10048-009-0202-4