Mitochondrial DNA variations in patients with maternally inherited diabetes and deafness syndrome
D Perucca-Lostanlen1, H Narbonne, J B Hernandez
1Laboratoire de Neurobiologie Cellulaire, UMR CNRS 6549 and Biostatistics and Medical Informatics Department, Faculté de Médecine, Avenue de Valombrose, Nice Cedex 02, 06107, France. perucca@unice.fr
Abstract:
Mitochondrial DNA (mtDNA) variants have been implicated in the pathogenesis of diabetes. A mutation in the tRNA leucine gene at position 3243 has been previously reported in mtDNA of maternally inherited diabetes and deafness (MIDD) patients. Because the true prevalence of the mitochondrial origin in diabetes may be underestimated, we searched for potentially diabetogenic anomalies of mtDNA in 9 patients highly suspected of mitochondrial diabetes selected on maternally inheritance and clinical features. In order to detect high levels of mutant DNA, the mtDNA of muscle sample of 2 patients was totally sequenced and the 22 tRNA genes and flanking sequences of 7 patients were analyzed. A new homoplasmic mutation at position 8381 was found in the ATPase 8 gene of mtDNA of a MIDD patient. The prevalence of three homoplasmic variations (G1888A, T4216G, A4917G) was significantly higher in the small group of MIDD patients compared to controls and other subjects groups. This study demonstrated in our patients sample the high frequency of homoplasmic variations, which could play a role by themselves or in combination, in the pathogenesis of diabetes.
Insights
Mitochondrial DNA variations are linked to diabetes. Researchers found new mutations and higher frequencies of known variations in patients with maternally inherited diabetes and deafness, suggesting a significant role in diabetes development.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Mitochondrial DNA (mtDNA) variants are increasingly recognized in diabetes pathogenesis.
- A specific mutation (3243) in the tRNA leucine gene is known in maternally inherited diabetes and deafness (MIDD).
- The prevalence of mitochondrial diabetes may be underestimated.
Purpose of the Study:
- To investigate potentially diabetogenic anomalies of mtDNA in patients with suspected mitochondrial diabetes.
- To analyze mtDNA in patients with maternal inheritance and specific clinical features.
Main Methods:
- Total sequencing of mtDNA from muscle samples of 2 patients.
- Analysis of 22 tRNA genes and flanking sequences in 7 patients.
- Comparison of mutation prevalence between MIDD patients and controls.
Main Results:
- A novel homoplasmic mutation at position 8381 in the ATPase 8 gene was identified in an MIDD patient.
- Three homoplasmic variations (G1888A, T4216G, A4917G) showed significantly higher prevalence in MIDD patients.
- High frequency of homoplasmic variations was observed in the patient sample.
Conclusions:
- Mitochondrial DNA variations are frequent in patients with suspected mitochondrial diabetes.
- These homoplasmic variations may contribute to diabetes pathogenesis individually or in combination.
- Further research is warranted to elucidate the role of mtDNA in diabetes development.
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