Abstract | BACKGROUND: METHODS: In seven families of various ethnic origins we assessed patients with progressive external ophthalmoplegia and unaffected individuals by clinical, biochemical, morphological, and molecular genetic characterisation and positron emission tomography (PET). FINDINGS: We recorded mutations in POLG in members of all seven families. Clinical assessment showed significant cosegregation of parkinsonism with POLG mutations (p<0.0001), and PET findings were consistent with dopaminergic neuron loss. Post-mortem examination in two individuals showed loss of pigmented neurons and pigment phagocytosis in substantia nigra without Lewy bodies. Furthermore, most women with progressive external ophthalmoplegia had early menopause-before age 35 years. The POLG gene defect resulted in secondary accumulation of mtDNA deletions in patients' tissues. INTERPRETATION: RELEVANCE TO PRACTICE:
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Authors | Petri Luoma, Atle Melberg, Juha O Rinne, Jyrki A Kaukonen, Nina N Nupponen, Richard M Chalmers, Anders Oldfors, Ilkka Rautakorpi, Leena Peltonen, Kari Majamaa, Hannu Somer, Anu Suomalainen |
Journal | Lancet (London, England)
(Lancet)
2004 Sep 4-10
Vol. 364
Issue 9437
Pg. 875-82
ISSN: 1474-547X [Electronic] England |
PMID | 15351195
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Mitochondrial
- DNA Polymerase gamma
- DNA-Directed DNA Polymerase
- POLG protein, human
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Topics |
- Adult
- Age of Onset
- Brain
(diagnostic imaging, pathology)
- DNA Polymerase gamma
- DNA, Mitochondrial
(genetics)
- DNA-Directed DNA Polymerase
(genetics)
- Female
- Humans
- Male
- Menopause, Premature
(genetics)
- Middle Aged
- Mutation
- Ophthalmoplegia, Chronic Progressive External
(complications, genetics)
- Parkinsonian Disorders
(complications, diagnostic imaging, genetics, pathology)
- Pedigree
- Sequence Analysis, DNA
- Tomography, Emission-Computed
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