Article Text
Abstract
Background: The 3243A→G MTTL1 mutation is the most common heteroplasmic mitochondrial DNA (mtDNA) mutation associated with disease. Previous studies have shown that the percentage of mutated mtDNA decreases in blood as patients get older, but the mechanisms behind this remain unclear.
Objectives and method: To understand the dynamics of the process and the underlying mechanisms, an accurate fluorescent assay was established for 3243A→G heteroplasmy and the amount of mtDNA in blood with real-time polymerase chain reaction was determined. The amount of mutated and wild-type mtDNA was measured at two time points in 11 subjects.
Results: The percentage of mutated mtDNA decreases exponentially during life, and peripheral blood leucocytes in patients harbouring 3243A→G are profoundly depleted of mtDNA.
Conclusions: A similar decrease in mtDNA has been seen in other mitochondrial disorders, and in 3243A→G cell lines in culture, indicating that depletion of mtDNA may be a common secondary phenomenon in several mitochondrial diseases. Depletion of mtDNA is not always due to mutation of a nuclear gene involved in mtDNA maintenance.
- GADPH, glyceraldehyde-3-phosphate dehydrogenase
- mtDNA, mitochondrial DNA
- PCR, polymerase chain reaction
- RFLP, restriction fragment length polymorphism
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Supplementary materials
Footnotes
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PFC is a Wellcome Trust Senior Fellow in Clinical Science.
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Funding: PFC also receives funding from Ataxia (UK), the Alzheimer’s Research Trust, the Association Française Contre les Myopathies, and the United Mitochondrial Diseases Foundation, and the EU FP P
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Competing interests: None declared.
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Published Online First 1 September 2006