POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe

• Published in: Movement disorders Vol. 25; no. 15; pp. 2678 - 2682
• Main Authors: Schicks, Julia, Synofzik, Matthis, Schulte, Claudia, Schöls, Ludger
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.11.2010; Wiley; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; ataxia; Biological and medical sciences; Cerebellar Ataxia - genetics; Child; Child, Preschool; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Helicases - genetics; DNA Polymerase gamma; DNA-Directed DNA Polymerase - genetics; epilepsy; Europe; European Continental Ancestry Group - genetics; Female; genetics; Humans; Infant; Male; Medical sciences; Middle Aged; mitochondrial; Mitochondrial Proteins; Movement disorders; Mutation; Neurology; Europe; Mitochondria; Nervous system diseases; genetics; ataxia; Cerebellar ataxia; Epilepsy; Central nervous system disease; mitochondrial; Cerebral disorder
• DOI: 10.1002/mds.23286
• ISSN: 0885-3185

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. © 2010 Movement Disorder Society.