A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA.
Open accessAbstract
BACKGROUND: Several families have been described in which a mutation of mitochondrial DNA, the substitution of guanine for adenine (A-->G) at position 3243 of leucine transfer RNA, is associated with diabetes mellitus and deafness. The prevalence, clinical features, and pathophysiology of diabetes with this mutation are largely undefined. METHODS: We studied 55 patients with insulin-dependent diabetes mellitus (IDDM) and a family history of diabetes (group 1), 85 patients with IDDM and no family history of diabetes (group 2), 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and a family history of diabetes (group 3), and 5 patients with diabetes and deafness (group 4) for the mutation. We also studied the prevalence and characteristics of diabetes in 39 patients with a syndrome consisting of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes who were known to have the mutation and 127 of their relatives (group 5). RESULTS: We identified 16 unrelated patients with diabetes associated with the A-->G mutation: 3 patients from group 1 (6 percent), 2 patients from group 3 (2 percent), 3 patients from group 4 (60 percent), and 8 patients from group 5 (21 percent). We also identified 16 additional subjects who had diabetes and the mutation among 42 relatives of the patients with diabetes and the mutation in groups 1, 2, 3, and 4 and 20 affected subjects among the 127 relatives of the patients in group 5. Diabetes cosegregated with the mutation in a fashion consistent with maternal transmission, was frequently (in 61 percent of cases) associated with sensory hearing loss, and was generally accompanied by impaired insulin secretion. CONCLUSIONS: Diabetes mellitus associated with the A-->G mutation at position 3243 of mitochondrial leucine transfer RNA represents a subtype of diabetes found in both patients with IDDM and patients with NIDDM in Japan.
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The 3243A>G mutation in the mtDNA-encoded tRNALeu, UUR gene is associated with maternally inherited diabetes and deafness (MIDD).
“Of these, the best studied is the 3243AϾG mutation in the mtDNA-encoded tRNALeu, UUR gene, which is associated with maternally inherited diabetes and deafness (MIDD) (243,244).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [243]
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- Authors
- Kadowaki, T., Kadowaki, H., Mori, Y., Tobe, K., Sakuta, R., Suzuki, Y., Tanabe, Y., Sakura, H., Awata, T., Goto, Y.-I., Hayakawa, T., Matsuoka, K., Kawamori, R., Kamada, T., Horai, S., Nonaka, I., Hagura, R., Akanuma, Y., & Yazaki, Y.
- Affiliations
- The University of Tokyo (JP)
- National Institute of Neuroscience (JP)
- Saiseikai Central Hospital (JP)
- Chiba Children's Hospital (JP)
- Jichi Medical University (JP)
- The University of Osaka (JP)
- National Institute of Genetics (JP)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1994-04-07
- Volume
- 330
- Issue
- 14
- Pages
- 962-968
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2338125871
- Cited by
- 551
- References
- 19
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 9 · 2021: 6 · 2020: 9 · 2019: 16 · 2018: 6 · 2017: 13 · 2016: 12 · 2015: 11 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 12.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- mitochondrial DNA mutations, A3243G mutation, diabetes mellitus, type 1 diabetes, type 2 diabetes, deafness, impaired insulin secretion, mother-to-child transmission
- MeSH terms
- Adolescent, Adult, Aged, Base Sequence, Child, Child, Preschool, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Female, Humans, Insulin Resistance, Leucine, Male, Middle Aged, Molecular Sequence Data, Mutation, Pedigree
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