Journal Article

Mitochondrial DNA polymerase-γ and human disease

Gavin Hudson and Patrick F. Chinnery

in Human Molecular Genetics

Volume 15, issue suppl_2, pages R244-R252
Published in print October 2006 | ISSN: 0964-6906
Published online October 2006 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddl233
Mitochondrial DNA polymerase-γ and human disease

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The maintenance of mitochondrial DNA (mtDNA) is critically dependent upon polymerase-γ (pol-γ), encoded by the nuclear gene POLG. Over the last 5 years, it has become clear that mutations of POLG are a major cause of human disease. Secondary mtDNA defects characterize these disorders, with mtDNA depletion, multiple mtDNA deletions or multiple point mutations of mtDNA in clinically affected tissues. The secondary mtDNA defects cause cell and tissue-specific deficiencies of mitochondrial oxidative phosphorylation, leading to organ dysfunction and human disease. Functional genetic variants of POLG are present in up to ∼0.5% of the general population, and pathogenic mutations have been described in most exons of the gene. Clinically, POLG mutations can present from early neonatal life to late middle age, with a spectrum of phenotypes that includes common neurological disorders such as migraine, epilepsy and Parkinsonism. Transgenic mice and biochemical studies of recombinant mutated proteins are helping to unravel mechanisms of pathogenesis, and patterns are beginning to emerge relating genotype to phenotype.

Journal Article.  5085 words.  Illustrated.

Subjects: Genetics and Genomics

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