Perucca-Lostanlen D, Narbonne H, Hernandez J B, Staccini P, Saunieres A, Paquis-Flucklinger V, Vialettes B, Desnuelle C
Laboratoire de Neurobiologie Cellulaire, UMR CNRS 6549 and Biostatistics and Medical Informatics Department, Faculté de Médecine, Avenue de Valombrose, Nice Cedex 02, 06107, France.
Biochem Biophys Res Commun. 2000 Nov 2;277(3):771-5. doi: 10.1006/bbrc.2000.3751.
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.
线粒体DNA（mtDNA）变异与糖尿病的发病机制有关。先前已在母系遗传糖尿病和耳聋（MIDD）患者的mtDNA中报道了位于3243位的tRNA亮氨酸基因突变。由于线粒体起源在糖尿病中的真实患病率可能被低估，我们在9例因母系遗传和临床特征而高度怀疑为线粒体糖尿病的患者中寻找mtDNA潜在的致糖尿病异常。为了检测高水平的突变DNA，对2例患者肌肉样本的mtDNA进行了全序列测定，并分析了7例患者的22个tRNA基因及其侧翼序列。在1例MIDD患者的mtDNA的ATPase 8基因中发现了一个位于8381位的新的纯合突变。与对照组和其他受试者组相比，一小群MIDD患者中三种纯合变异（G1888A、T4216G、A4917G）的患病率显著更高。这项研究在我们的患者样本中证明了纯合变异的高频率，它们可能单独或联合在糖尿病的发病机制中起作用。
