title: The heteroplasmic m.14709T>C mutation in the tRNA(Glu) gene in two Tunisian families with mitochondrial diabetes.
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.
  
  
  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.
authors.affiliation: Faculty of Medicine of Sfax, Human Molecular Genetic Laboratory, Sfax, Tunisia.
authors.forename: Najla
authors.initials: N
authors.lastname: Mezghani
authors.forename: Emna
authors.initials: E
authors.lastname: Mkaouar-Rebai
authors.forename: Mouna
authors.initials: M
authors.lastname: Mnif
authors.forename: Nadia
authors.initials: N
authors.lastname: Charfi
authors.forename: Nabila
authors.initials: N
authors.lastname: Rekik
authors.forename: Saoussan
authors.initials: S
authors.lastname: Youssef
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012352:RNA, Transfer, Glu / Q000235:genetics*; D014416:Tunisia; D055815:Young Adult
chemical_list: D012352:RNA, Transfer, Glu