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 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 0340-5354 1432-1459 |
DOI: | 10.1007/s00415-013-7132-7 |