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Lookup NU author(s): Professor Gavin Hudson, Professor Patrick Chinnery
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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. © 2006 Oxford University Press.
Author(s): Hudson G, Chinnery PF
Publication type: Review
Publication status: Published
Journal: Human Molecular Genetics
Year: 2006
Volume: 15
Issue: Review Issue 2
Pages: R244-R252
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
URL: http://dx.doi.org/10.1093/hmg/ddl233
DOI: 10.1093/hmg/ddl233
