title: Mitochondrial DNA variations in patients with maternally inherited diabetes and deafness syndrome.
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.
authors.affiliation: Laboratoire 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
authors.forename: D
authors.initials: D
authors.lastname: Perucca-Lostanlen
authors.forename: H
authors.initials: H
authors.lastname: Narbonne
authors.forename: J B
authors.initials: JB
authors.lastname: Hernandez
authors.forename: P
authors.initials: P
authors.lastname: Staccini
authors.forename: A
authors.initials: A
authors.lastname: Saunieres
authors.forename: V
authors.initials: V
authors.lastname: Paquis-Flucklinger
authors.forename: B
authors.initials: B
authors.lastname: Vialettes
authors.forename: C
authors.initials: C
authors.lastname: Desnuelle
mesh_terms: D000328:Adult; D000368:Aged; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial