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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2011-1-24
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pubmed:abstractText |
Disorders of mitochondrial DNA (mtDNA) maintenance have emerged as an important cause of human genetic disease, but demonstrating the functional consequences of de novo mutations remains a major challenge. We studied the rate of depletion and repopulation of mtDNA in human fibroblasts exposed to ethidium bromide in patients with heterozygous POLG mutations, POLG2 and TK2 mutations. Ethidium bromide induced mtDNA depletion occurred at the same rate in human fibroblasts from patients and healthy controls. By contrast, the restoration of mtDNA levels was markedly delayed in fibroblasts from patients with compound heterozygous POLG mutations. Specific POLG2 and TK2 mutations did not delay mtDNA repopulation rates. These observations are consistent with the hypothesis that mutations in POLG impair mtDNA repopulation within intact cells, and provide a potential method of demonstrating the functional consequences of putative pathogenic alleles causing a defect of mtDNA synthesis.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-3002
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pubmed:author |
pubmed-author:ChinneryPatrick FPF,
pubmed-author:HallmannKerstinK,
pubmed-author:HorvathRitaR,
pubmed-author:KunzWolfram SWS,
pubmed-author:PyleAngelaA,
pubmed-author:SamuelsDavid CDC,
pubmed-author:SchoelerSusanneS,
pubmed-author:SitarzKamil SKS,
pubmed-author:StewartJoanna DJD,
pubmed-author:TaylorRobert WRW,
pubmed-author:Yu-Wai-ManPatrickP
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier B.V. All rights reserved.
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pubmed:issnType |
Print
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pubmed:volume |
1812
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
321-5
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pubmed:dateRevised |
2011-4-1
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pubmed:meshHeading |
pubmed-meshheading:21138766-Adult,
pubmed-meshheading:21138766-Amino Acid Substitution,
pubmed-meshheading:21138766-Case-Control Studies,
pubmed-meshheading:21138766-DNA, Mitochondrial,
pubmed-meshheading:21138766-DNA Replication,
pubmed-meshheading:21138766-DNA-Directed DNA Polymerase,
pubmed-meshheading:21138766-Diffuse Cerebral Sclerosis of Schilder,
pubmed-meshheading:21138766-Enzyme Inhibitors,
pubmed-meshheading:21138766-Epilepsy,
pubmed-meshheading:21138766-Ethidium,
pubmed-meshheading:21138766-Female,
pubmed-meshheading:21138766-Fibroblasts,
pubmed-meshheading:21138766-Heterozygote,
pubmed-meshheading:21138766-Homozygote,
pubmed-meshheading:21138766-Humans,
pubmed-meshheading:21138766-Infant,
pubmed-meshheading:21138766-Male,
pubmed-meshheading:21138766-Mitochondria,
pubmed-meshheading:21138766-Muscular Diseases,
pubmed-meshheading:21138766-Mutation,
pubmed-meshheading:21138766-Thymidine Kinase
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pubmed:year |
2011
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pubmed:articleTitle |
POLG mutations cause decreased mitochondrial DNA repopulation rates following induced depletion in human fibroblasts.
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pubmed:affiliation |
Mitochondrial Research Group, Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Case Reports,
Research Support, Non-U.S. Gov't
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