Cited by 69Mitochondrial Function and PathologyGenetic Associations and EpidemiologyMetabolism and Genetic Disorders

A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic mutation for maternally inherited type 2 diabetes.

Tawata, M, Hayashi, J I, Isobe, K, Ohkubo, E, Ohtaka, M, Chen, J, Aida, K, Onaya, T·2000·Diabetes

Abstract

From a family of 16 diabetic patients with typical maternal inheritance, we investigated a 69-year-old woman with type 2 diabetes. The proband showed no major deletions in the mitochondrial DNA (mtDNA). Direct sequencing revealed 7 missense and 5 ribosomal RNA homoplasmic nucleotide substitutions when compared with the Cambridge Sequence and its recent revision. When compared with the control cybrid cells, the proband cybrid cells showed 6 nucleotide substitutions. Among these, 14577 T/C, which turned out to be 98.9% heteroplasmic, is a new missense substitution in the NADH dehydrogenase 6 gene. We also observed 2 other patients with 14577 T/C substitution from another group of 252 unrelated diabetic patients, whereas no individual from a group of 529 control subjects had 14577 T/C substitution. Furthermore, these 6 substitutions were in linkage disequilibrium. Mitochondrial respiratory chain complex I activity and O2 consumption rates of the proband cybrid cells, which were obtained by the fusion of mtDNA-deleted (rho0) HeLa cells and mtDNA from the proband, showed 64.5 and 61.5% reductions, respectively, compared with control cybrid cells. The present study strongly indicates that the new mtDNA mutation at 14577 T/C is probably a major pathogenic mutation for type 2 diabetes in this family.

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Crossref · 10.2337/diabetes.49.7.1269

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  • Mutation 14577 T>C, a missense substitution in the NADH dehydrogenase 6 gene, is another example of an mtDNA mutation associated with diabetes.

    “Another example is mutation 14577 TϾC, a missense substitution in the NADH dehydrogenase 6 gene (245).”
  • In hybrid cell lines derived from probands with the 14577 T>C mutation, mitochondrial respiratory chain complex I activity and O2 consumption rates are decreased by 65 and 62%, respectively.

    “In this case, mitochondrial respiratory chain complex I activity and O 2 consumption rates are decreased by 65 and 62%, respectively, in hybrid cell lines derived from probands.”

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Authors
Tawata, M., Hayashi, J. I., Isobe, K., Ohkubo, E., Ohtaka, M., Chen, J., Aida, K., & Onaya, T.
Affiliations
Third Department of Internal Medicine, Yamanashi Medical University, Tamaho, Japan. tawatam@res.yamanashi-med.ac.jp
Venue
Diabetes
Published
2000-07-01
Volume
49
Issue
7
Pages
1269-1272
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2114101869
Cited by
69
References
20
Citations by year
2026: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 1 · 2014: 1 · 2013: 2 · 2012: 3
FWCI
1.93
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
mitochondrial DNA mutations, type 2 diabetes, ND6, missense substitutions, cybrid cells, oxygen consumption, linkage disequilibrium, pathogenic variants
MeSH terms
Aged, Cytochrome b Group, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Female, HeLa Cells, Humans, Hybrid Cells, Male, Mitochondria, NADH Dehydrogenase, Oxygen Consumption, Pedigree, RNA, Ribosomal, RNA, Ribosomal, 16S, Genomic Imprinting, Mutation, Missense

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