The heteroplasmic m.14709T>C mutation in the tRNA(Glu) gene in two Tunisian families with mitochondrial diabetes

J Diabetes Complications. Jul-Aug 2010;24(4):270-7. doi: 10.1016/j.jdiacomp.2009.11.002. Epub 2010 Jan 4.

Abstract

Diabetes mellitus (DM) is a heterogeneous disorder characterized by the presence of chronic hyperglycemia. Genetic factors play an important role in the development of this disorder, and several studies reported mutations in nuclear genes implicated in the insulin function. Besides, DM can be maternally transmitted in some families, possibly due to the maternal mitochondrial inheritance. In fact, mitochondrial genes may be plausible causative agents for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells.

Materials and methods: In this report, we screened two Tunisian families with mitochondrial diabetes for the m.3243A>G and the m.14709T>C mutations, respectively, in the tRNA(Leu(UUR)) and the tRNA(Glu) genes.

Results: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequence-specific primers by polymerase chain reaction (SSP-PCR) analysis in the leucocytes and the buccal mucosa in the members of the two families showed the absence of the m.3243A>G mutation and the presence of the heteroplasmic m.14709T>C mutation in the tRNA(Glu) gene in the two tested tissues.

Conclusions: We conclude that the m.14709T>C mutation in the tRNA(Glu) gene could be a cause of mitochondrial diabetes in Tunisian affected families. In addition, the heteroplasmic loads correlated with the severity and the onset of mitochondrial diabetes in one family but not in the other, suggesting the presence of environmental factors or nuclear modifier genes.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 2 / genetics*
  • Family
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Diseases / genetics*
  • Pedigree
  • Point Mutation* / physiology
  • Polymorphism, Single Nucleotide / physiology
  • RNA, Transfer, Glu / genetics*
  • Tunisia
  • Young Adult

Substances

  • RNA, Transfer, Glu