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

Federica Invernizzi, Sara Varanese, Astrid Thomas, Franco Carrara, Marco Onofrj, Massimo Zeviani

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)460-464
Number of pages5
JournalNeuromuscular Disorders
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 2008

Fingerprint

Chronic Progressive External Ophthalmoplegia
Parkinsonian Disorders
Levodopa
Tremor
Mitochondrial DNA
Mutation
Diffuse Cerebral Sclerosis of Schilder
pol Genes
Corpus Striatum
Dopamine Agonists
DNA-Directed DNA Polymerase
Ataxia
Parkinson Disease
Epilepsy
Dopamine
Catalytic Domain

Keywords

  • Mitochondrial DNA
  • Multiple mtDNA deletions
  • Parkinsonism
  • Polymerase gamma
  • Progressive external ophthalmoplegia

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism. / Invernizzi, Federica; Varanese, Sara; Thomas, Astrid; Carrara, Franco; Onofrj, Marco; Zeviani, Massimo.

In: Neuromuscular Disorders, Vol. 18, No. 6, 06.2008, p. 460-464.

Research output: Contribution to journalArticle

Invernizzi, Federica ; Varanese, Sara ; Thomas, Astrid ; Carrara, Franco ; Onofrj, Marco ; Zeviani, Massimo. / Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism. In: Neuromuscular Disorders. 2008 ; Vol. 18, No. 6. pp. 460-464.
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