Variations of mitochondrial DNA polymerase γ in patients with Parkinson’s disease

Parkinson’s disease is associated with mitochondrial dysfunction. The POLG1 gene encodes DNA-polymerase γ, which is responsible for the replication of mitochondrial DNA. Mutations in POLG1 cause neurodegenerative diseases such as progressive external ophthalmoplegia and Alpers syndrome. In this stud...

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Veröffentlicht in:Journal of neurology 2013-12, Vol.260 (12), p.3144-3149
Hauptverfasser: Ylönen, S., Ylikotila, P., Siitonen, A., Finnilä, S., Autere, J., Majamaa, K.
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container_end_page 3149
container_issue 12
container_start_page 3144
container_title Journal of neurology
container_volume 260
creator Ylönen, S.
Ylikotila, P.
Siitonen, A.
Finnilä, S.
Autere, J.
Majamaa, K.
description Parkinson’s disease is associated with mitochondrial dysfunction. The POLG1 gene encodes DNA-polymerase γ, which is responsible for the replication of mitochondrial DNA. Mutations in POLG1 cause neurodegenerative diseases such as progressive external ophthalmoplegia and Alpers syndrome. In this study, we investigated if mutations in POLG1 had any correlation with Parkinson’s disease. Subjects consisted of Finnish patients with early-onset Parkinson’s disease (EOPD, N  = 441) or late-onset Parkinson’s disease (LOPD, N  = 263). The POLG1 gene was screened for nine previously known mutations. Two patients were compound heterozygotes with respect to putatively pathogenic alleles. Twenty-eight patients harbored a heterozygous missense mutation, but the allele frequencies did not differ from those of the controls. Interestingly, the frequency of affected siblings was 4.6-fold higher (95 % confidence interval; 1.09, 19.5) among the patients with EOPD and with heterozygous POLG1 mutations than among patients without mutations. Clinically the patients with or without POLG1 mutations did not differ from each other. Our findings provide two lines of evidence suggesting a role for POLG1 mutations in Parkinson’s disease: (1) identification of patients with compound heterozygous mutations in POLG1 , and (2) higher frequency of affected siblings among the EOPD patients with heterozygous POLG1 mutations than among EOPD patients without mutations.
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The POLG1 gene encodes DNA-polymerase γ, which is responsible for the replication of mitochondrial DNA. Mutations in POLG1 cause neurodegenerative diseases such as progressive external ophthalmoplegia and Alpers syndrome. In this study, we investigated if mutations in POLG1 had any correlation with Parkinson’s disease. Subjects consisted of Finnish patients with early-onset Parkinson’s disease (EOPD, N  = 441) or late-onset Parkinson’s disease (LOPD, N  = 263). The POLG1 gene was screened for nine previously known mutations. Two patients were compound heterozygotes with respect to putatively pathogenic alleles. Twenty-eight patients harbored a heterozygous missense mutation, but the allele frequencies did not differ from those of the controls. Interestingly, the frequency of affected siblings was 4.6-fold higher (95 % confidence interval; 1.09, 19.5) among the patients with EOPD and with heterozygous POLG1 mutations than among patients without mutations. 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subjects Adult
Age
Aged
DNA Polymerase gamma
DNA-Directed DNA Polymerase - genetics
Female
Humans
Male
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neurology
Neuroradiology
Neurosciences
Original Communication
Parkinson Disease - enzymology
Parkinson Disease - genetics
Pedigree
Polymorphism, Restriction Fragment Length
title Variations of mitochondrial DNA polymerase γ in patients with Parkinson’s disease
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