A1 Refereed original research article in a scientific journal
Variations of mitochondrial DNA polymerase gamma in patients with Parkinson's disease
Authors: Ylönen S, Ylikotila P, Siitonen A, Finnilä S, Autere J, Majamaa K
Publisher: SPRINGER HEIDELBERG
Publishing place: HEIDELBERG; TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
Publication year: 2013
Journal: Journal of Neurology
Journal name in source: Journal of neurology
Journal acronym: J.Neurol.
Volume: 260
Issue: 12
First page : 3144
Last page: 3149
Number of pages: 6
ISSN: 0340-5354
DOI: https://doi.org/10.1007/s00415-013-7132-7
Abstract
Parkinson's disease is associated with mitochondrial dysfunction. The POLG1 gene encodes DNA-polymerase gamma, 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.
Parkinson's disease is associated with mitochondrial dysfunction. The POLG1 gene encodes DNA-polymerase gamma, 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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