Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Université de Sfax, Tunisia.
Biochem Biophys Res Commun. 2013 Feb 22;431(4):670-4. doi: 10.1016/j.bbrc.2013.01.063. Epub 2013 Jan 26.
Maternally inherited diabetes and deafness (MIDD) is a mitochondrial syndrome characterized by the onset of sensorineural hearing loss and diabetes in adults. Some patients may have other additional clinical features common in mitochondrial disorders such as pigmentary retinopathy, ptosis, cardiomyopathy, myopathy and renal affections. We report a 40-year-old Tunisian patient presenting maternally inherited type 2 diabetes and deafness (MIDD). A molecular genetic analysis was conducted in the patient and his twin sister, but no reported mutations in the tRNA(Leu(UUR)) and tRNA(Glu) genes were found, especially the two mitochondrial m.3243A>G and the m.14709T>C mutations in muscle and blood leukocytes. The results showed the presence of the mitochondrial NADH deshydrogenase 1 (ND1) homoplasmic m.3308T>C mutation the 2 tested tissues (blood leukocytes and skeletal muscle) of the proband and in the patient's sister blood leukocytes. In addition, we identified the mitochondrial 12S rRNA m.1555A>G mutation in muscle and blood leukocytes. The Long-range PCR amplification revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of MIDD in whom we detected the 12S rRNA m.1555A>G and the ND1 m.3308T>C mutations with mitochondrial multiple deletions.
母系遗传糖尿病伴耳聋(MIDD)是一种线粒体综合征,其特征是成年后出现感音神经性听力损失和糖尿病。一些患者可能还有其他常见于线粒体疾病的附加临床特征,如色素性视网膜炎、上睑下垂、心肌病、肌病和肾脏疾病。我们报告了一例 40 岁的突尼斯患者,表现为母系遗传 2 型糖尿病伴耳聋(MIDD)。对患者及其双胞胎妹妹进行了分子遗传学分析,但未发现 tRNA(Leu(UUR))和 tRNA(Glu)基因报告的突变,特别是肌肉和血液白细胞中的两个线粒体 m.3243A>G 和 m.14709T>C 突变。结果显示,在 2 种测试组织(血液白细胞和骨骼肌)中存在线粒体 NADH 脱氢酶 1(ND1)同质突变 m.3308T>C ,以及患者妹妹的血液白细胞中存在该突变。此外,我们在肌肉和血液白细胞中鉴定出线粒体 12S rRNA m.1555A>G 突变。长距离 PCR 扩增显示,从患者骨骼肌中提取的线粒体 DNA 存在多个缺失,去除了几个 tRNA 和编码蛋白的基因。我们的研究报告了一例具有 MIDD 临床特征的突尼斯患者,我们在该患者中检测到 12S rRNA m.1555A>G 和 ND1 m.3308T>C 突变,并伴有线粒体多处缺失。