Document Detail

The 8993 mtDNA mutation: heteroplasmy and clinical presentation in three families.
MedLine Citation:
PMID:  8044652     Owner:  NLM     Status:  MEDLINE    
The point mutation at bp 8993 of human mtDNA in the ATPase 6 gene is associated with neurogenic weakness, ataxia and retinitis pigmentosa, and with subacute necrotizing encephalomyelopathy (Leigh disease) when present at high copy number. In this study we describe three new multiplex families with the ATPase 8993 mtDNA mutation and demonstrate a correlation between the percentage heteroplasmy of this mutation and the clinical phenotype. By combining this study with previous data we produce a graph of age of onset of symptoms versus percentage heteroplasmy of the mutation. Finally, we determine that ATP synthesis with NAD-linked substrates in cultured lymphoblast mitochondria from three patients with Leigh disease who had a high percentage heteroplasmy was on average 66% of the rate seen in control lymphoblast mitochondria. Similar rates are observed in lymphoblast mitochondria isolated from patients with Leigh disease due to complex I deficiency. This percentage appears to be independent of the rate of electron transport in mitochondria from patient cell lines with the mtDNA 8993 mutation.
Y Tatuch; R A Pagon; B Vlcek; R Roberts; M Korson; B H Robinson
Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  2     ISSN:  1018-4813     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  1994  
Date Detail:
Created Date:  1994-08-30     Completed Date:  1994-08-30     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  35-43     Citation Subset:  IM    
Department of Biochemistry, University of Toronto, Ont., Canada.
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MeSH Terms
Adenosine Triphosphatases / deficiency,  genetics
Adenosine Triphosphate / biosynthesis
Age of Onset
Base Sequence
DNA Primers
DNA, Mitochondrial / genetics*,  metabolism
Electron Transport
Gene Expression
Genetic Variation
Leigh Disease / genetics*,  metabolism
Mitochondrial Encephalomyopathies / genetics*,  metabolism
Molecular Sequence Data
Multigene Family
Oxidative Phosphorylation
Point Mutation*
Retinitis Pigmentosa / genetics
Reg. No./Substance:
0/DNA Primers; 0/DNA, Mitochondrial; 56-65-5/Adenosine Triphosphate; EC 3.6.1.-/Adenosine Triphosphatases

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