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 language | English |
|---|---|
| Pages (from-to) | 460-464 |
| Number of pages | 5 |
| Journal | Neuromuscular Disorders |
| Volume | 18 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism
AU - Invernizzi, Federica
AU - Varanese, Sara
AU - Thomas, Astrid
AU - Carrara, Franco
AU - Onofrj, Marco
AU - Zeviani, Massimo
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Mitochondrial DNA
KW - Multiple mtDNA deletions
KW - Parkinsonism
KW - Polymerase gamma
KW - Progressive external ophthalmoplegia
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UR - http://www.scopus.com/inward/citedby.url?scp=45449101303&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2008.04.005
DO - 10.1016/j.nmd.2008.04.005
M3 - Article
C2 - 18502641
AN - SCOPUS:45449101303
VL - 18
SP - 460
EP - 464
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 6
ER -