Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism.

TitleTwo novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism.
Publication TypeJournal Article
Year of Publication2008
AuthorsInvernizzi, F, Varanese, S, Thomas, A, Carrara, F, Onofrj, M, Zeviani, M
JournalNeuromuscul Disord
Volume18
Issue6
Pagination460-4
Date Published2008 Jun
ISSN0960-8966
KeywordsDNA Mutational Analysis, DNA Polymerase gamma, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Humans, Male, Middle Aged, Mutation, Ophthalmoplegia, Chronic Progressive External, Parkinsonian Disorders, Sequence Analysis, Protein, Tremor
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.

DOI10.1016/j.nmd.2008.04.005
Alternate JournalNeuromuscul. Disord.
Citation Key10.1016/j.nmd.2008.04.005
PubMed ID18502641
Grant ListGGP07019 / / Telethon / Italy