Parkinsonism, premature menopause, and mitochondrial DNA polymerase [gamma] mutations: clinical and molecular genetic study

Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ophthalmoplegia-and multiple deletions of mtDNA. Mitochondrial dysfu...

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Bibliographic Details
Published in:The Lancet (British edition) 2004-09, Vol.364 (9437), p.875
Main Authors: Luoma, Petri, Melberg, Atle, Rinne, Juha O, Kaukonen, Jyrki A
Format: Article
Language:English
Subjects:
Accumulation
ATP
Biodegradation
Clinical trials
Enzymes
Genetics
Hearing loss
Menopause
Mitochondrial DNA
Mutation
Oxidative stress
Parkinson's disease
Pathology
Proteins
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Summary:Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ophthalmoplegia-and multiple deletions of mtDNA. Mitochondrial dysfunction is also suspected to participate in the pathogenesis of Parkinson's disease. However, no primary gene defects affecting mitochondrial proteins causing mendelian transmission of parkinsonism have been characterised. We aimed to analyse the gene sequence of POLG in patients with progressive external ophthalmoplegia and their healthy relatives. 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). We recorded mutations in POLG in members of all seven families. Clinical assessment showed significant cosegregation of parkinsonism with POLG mutations (p
ISSN:0140-6736
1474-547X