A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies
Abstract
Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).
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Over 80% of patients with MELAS have the m.3243A>G mutation in the MT-TL1 gene.
“Over 80% of patients with MELAS have the m.3243A N G mutation in the MT-TL1 gene [109,110].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [109]
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- Authors
- Goto, Y.-I., Nonaka, I., & Horai, S.
- Affiliations
- National Center of Neurology and Psychiatry (JP)
- National Institute of Genetics (JP)
- ORCID
- Goto, Yu-ichi
- Venue
- Nature
- Published
- 1990-12
- Volume
- 348
- Issue
- 6302
- Pages
- 651-653
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2045409504
- Cited by
- 2,070
- References
- 25
- Citations by year
- 2026: 36 · 2025: 60 · 2024: 55 · 2023: 55 · 2022: 68 · 2021: 62 · 2020: 63 · 2019: 50 · 2018: 52 · 2017: 52 · 2016: 52 · 2015: 44 · 2014: 47 · 2013: 55 · 2012: 63
- FWCI
- 21.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- 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 encephalomyopathy, mitochondrial DNA mutations, dihydrouridine loop, molecular diagnosis, heteroplasmy, Kearns-Sayre syndrome, MERRF, chronic progressive external ophthalmoplegia, mitochondrial myopathy
- MeSH terms
- Base Sequence, Brain Diseases, Humans, Male, Mitochondria, Muscle, Molecular Sequence Data, Mutation, Reference Values, RNA, Transfer, Leu, Sequence Homology, Nucleic Acid, Restriction Mapping
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