Decrease of 3243 A–>G mtDNA mutation from blood in MELAS syndrome: a longitudinal study
Open accessAbstract
It is widely held that changes in the distribution of mutant mtDNAs underlie the progressive nature of mtDNA diseases, but there are few data documenting such changes. We compared the levels of 3243 A-->G mutant mtDNA in blood at birth from Guthrie cards and at the time of diagnosis in a blood DNA sample from patients with mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) syndrome. Paired blood DNA samples separated by 9-19 years were obtained from six patients with MELAS. Quantification of mutant load, by means of a solid-phase minisequencing technique, demonstrated a decline (range 12%-29%) in the proportion of mutant mtDNA in all cases (P=.0015, paired t-test). These results suggest that mutant mtDNA is slowly selected from rapidly dividing blood cells in MELAS.
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An average annual 1% decrease in m.3243A>G mutation levels in blood has been described.
“For example, an average annual 1% decrease in m.3243A N G mutation levels in blood has been described [63].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [63]
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- Authors
- Rahman, S., Poulton, J., Marchington, D., & Suomalainen, A.
- Affiliations
- John Radcliffe Hospital (GB)
- Corresponding author
- Poulton, J.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 68
- Issue
- 1
- Pages
- 238-240
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1234919
- OpenAlex
- W1994003350
- Cited by
- 237
- References
- 20
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 5 · 2021: 12 · 2020: 13 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 8 · 2015: 8 · 2014: 15 · 2013: 8 · 2012: 13
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- MELAS, mitochondrial DNA, blood, mitochondrial encephalopathy, lactic acidosis
- MeSH terms
- Adolescent, Adult, Child, DNA Mutational Analysis, DNA, Mitochondrial, Humans, Infant, Newborn, Longitudinal Studies, Mutation, Time Factors, MELAS Syndrome, Sequence Analysis, DNA
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