Résumé :
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Communication n° 317. Autosomal dominant progressive external opththalmoplegia (adPEO) is characterized by ptosis and weakness of the extraocular muscles. Mutations within several nuclear genes (ANT1, C10orf2, POLG) were recently discovered to be at the origin of adPEO. Mutations in these genes are typically associated with multiple mitochondrial deletions in post-mitotic tissues and impaired functioning of mitochondrial oxidative phosphorylation. Here we report three Belgian families presenting with adPEO, two of them carrying a C10orf2 mutation and one family carrying a POLG mutation. Within the first two families 5 patients suffered from isolated progressive external ophthalmoplegia. All affected patients presented with an heterozygous A359T C10orf2 mutation. Within the third family one patient suffered from ptosis, external ophthalmoplegia, together with ataxia, polyneuropathy and myopathy leading to dysphagia and respiratory failure. She was carrying a dominant POLG Y955C mutation typically associated with a more severe phenotype. C10orf2 encodes Twinkle, a protein functioning as a mitochondrial helicase, which is probably involved in mitochondrial DNA replication and transcription. POLG encodes the alpha subunit of polymerase gamma required for mtDNA replication. Mutations in Twinkle have been associated with dominant or sporadic cases of PEO and mutations in POLG can cause either adPEO or arPEO. The clinical phenotypes of patients with POLG mutations are more heterogeneous and more severe than with Twinkle mutations.
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