title: POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe.
abstract: Nuclear genes, in particular mitochondrial polymerase gamma (POLG) and PEO1, have been increasingly recognized to cause mitochondrial diseases. Both genes assume a complementary role as part of the mitochondrial DNA (mtDNA) replication fork and, accordingly, seem to present with largely overlapping phenotypical spectra. We assessed the frequency and phenotypic spectrum of PEO1 compared to POLG mutations in a cohort of 80 patients with cerebellar ataxia for which common repeat expansion diseases had been excluded. Patients were selected to present additional features previously described for PEO1 mutations, namely early age of onset, progressive external ophthalmoplegia (PEO), or epilepsy. Whereas PEO1 mutations were not found in our cohort, POLG frequently caused ataxia with PEO (47%), psychiatric comorbidities (20%) and, more rarely, with epilepsy (14%). Thus, PEO1 is rare in Central Europe even in those patients displaying characteristic phenotypic features. In contrast, POLG is rather common in Central European ataxia patients. It should be particularly considered in ataxia patients with PEO, psychiatric comorbidities, and/or sensory neuropathy, even if characteristic mitochondrial extra-CNS features are absent.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, and German Research Centre of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Schicks
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
mesh_terms: D000293:Adolescent; D000328:Adult; D002524:Cerebellar Ataxia / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009154:Mutation; D044465:White People / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D004265:DNA Helicases; C431576:TWNK protein, human