The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
A functionally dominant mitochondrial DNA mutation
Open accessAbstract
Mutations in mitochondrial DNA (mtDNA) tRNA genes can be considered functionally recessive because they result in a clinical or biochemical phenotype only when the percentage of mutant molecules exceeds a critical threshold value, in the range of 70-90%. We report a novel mtDNA mutation that contradicts this rule, since it caused a severe multisystem disorder and respiratory chain (RC) deficiency even at low levels of heteroplasmy. We studied a 13-year-old boy with clinical, radiological and biochemical evidence of a mitochondrial disorder. We detected a novel heteroplasmic C>T mutation at nucleotide 5545 of mtDNA, which was present at unusually low levels (<25%) in affected tissues. The pathogenic threshold for the mutation in cybrids was between 4 and 8%, implying a dominant mechanism of action. The mutation affects the central base of the anticodon triplet of tRNA(Trp) and it may alter the codon specificity of the affected tRNA. These findings introduce the concept of dominance in mitochondrial genetics and pose new diagnostic challenges, because such mutations may easily escape detection. Moreover, similar mutations arising stochastically and accumulating in a minority of mtDNA molecules during the aging process may severely impair RC function in cells.
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“To complicate matters further, a dominant mt-tRNA mutation, m.5545C N T in the MT-TW gene, was recently reported with levels of mutation at b25% in clinically affected tissues [83].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [83]
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Kelly, R. D., Mahmud, A., & John, J. C. S. (2012) · Humana Press eBooks · doi:10.1007/978-1-62703-101-1_7
Mitochondrial disease during infancy and childhood
Saneto, R. P. (2016) · Journal of Pediatric Biochemistry · doi:10.3233/jpb-140127
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Holt, I. J., & Spinazzola, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819656-4.00009-7
Mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations
Pitceathly, R. D. S., & Rahman, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819656-4.00014-0
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(2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32832a7e09
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Chiaratti, M. R. (2010) · doi:10.47749/t/unicamp.2010.773702 · Cited by 1
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Durası, İ. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18858-9.00004-4
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A novel mitochondrial DNA deletion in molar–incisor periodontitis
Guo, Y., Wang, X., Liu, X., Zhang, J., & 栾庆先 (2026) · European journal of medical research · doi:10.1186/s40001-026-04394-w
Emerging therapeutic strategies for mitochondrial DNA-related diseases
Shi, R., Falabella, M., Aref, J., Hanna, M. G., Minczuk, M. A., Viscomi, C. F., & Pitceathly, R. D. S. (2026) · Cell Reports Medicine · doi:10.1016/j.xcrm.2026.102841
Metadata
- Authors
- Sacconi, S., Salviati, L., Nishigaki, Y., Walker, W. F., Hernandez-Rosa, E., Trevisson, E., Delplace, S., Desnuelle, C., Shanske, S., Hirano, M., Schon, E. A., Bonilla, E., De Vivo, D. C., DiMauro, S., & Davidson, M. M.
- Affiliations
- Inserm (FR)
- University of Padua (IT)
- Columbia University (US)
- Corresponding author
- Salviati, L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-03-04
- Volume
- 17
- Issue
- 12
- Pages
- 1814-1820
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC2900892
- OpenAlex
- W2150656083
- Cited by
- 113
- References
- 28
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 11 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 13
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P01NS011766)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD32062, R01HD057543, P01HD032062)
- 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
- mitochondrial DNA mutations, heteroplasmy, respiratory chain deficiency, mitochondrial disease, cybrids, codon specificity, multisystem disease
- MeSH terms
- Adolescent, Base Sequence, DNA, Mitochondrial, Fibroblasts, Humans, Male, Mitochondria, RNA, Transfer, Trp, Protein Biosynthesis, Point Mutation, Muscle, Skeletal, Mitochondrial Diseases
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