Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism
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- 作者：Federica Invernizzi ; Sara Varanese ; Astrid Thomas ; Franco Carrara ; Marco Onofrj ; Massimo Zeviani
- 关键词：Progressive external ophthalmoplegia ; Parkinsonism ; Polymerase gamma ; Mitochondrial DNA ; Multiple mtDNA deletions
- 刊名：Neuromuscular Disorders
- 出版年：2008
- 出版时间：June 2008
- 年：2008
- 卷：18
- 期：6
- 页码：460-464
- 全文大小：675 K
文摘
Different mutations, or combinations of mutations, in POLG1, the gene encoding pol γA, 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.