title: Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism.
abstract: Different mutations, or combinations of mutations, in POLG1, the gene encoding pol gammaA, the catalytic subunit of mitochondrial DNA polymerase, are associated with a spectrum of clinical presentations including autosomal dominant or recessive progressive external ophthalmoplegia (PEO), juvenile-onset ataxia and epilepsy, and Alpers-Huttenlocher syndrome. Parkinsonian features have been reported as a late complication of POLG1-associated dominant PEO. Good response to levodopa or dopamine agonists, reduced dopamine uptake in the corpus striatum and neuronal loss of the Substantia Nigra pars compacta have been documented in a few cases. Here we report two novel mutations in POLG1 in a compound heterozygous patient with autosomal recessive PEO, followed by pseudo-orthostatic tremor evolving into levodopa-responsive parkinsonism. These observations support the hypothesis that mtDNA dysfunction is engaged in the pathogenesis of idiopathic Parkinson's disease.
authors.affiliation: Unit of Molecular Neurogenetics, Pierfranco e Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, C. Besta Neurological Institute Foundation-IRCCS, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.forename: Sara
authors.initials: S
authors.lastname: Varanese
authors.forename: Astrid
authors.initials: A
authors.lastname: Thomas
authors.forename: Franco
authors.initials: F
authors.lastname: Carrara
authors.forename: Marco
authors.initials: M
authors.lastname: Onofrj
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000150:complications / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000150:complications / Q000235:genetics*; D020539:Sequence Analysis, Protein; D014202:Tremor / Q000150:complications / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human