Vialettes B, Paquis-Fluckinger V, Silvestre-Aillaud P, Ben Dahan D, Pelissier J F, Etchary-Bouyx F, Raccah D, Gin H, Guillausseau P J, Vanuxen D
Département de Nutrition, Université de Marseille, France.
Diabetes Care. 1995 Jul;18(7):1023-8. doi: 10.2337/diacare.18.7.1023.
A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina.
Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects.
This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical "salt and pepper" pigmentary retinopathy was observed without consequences on visual acuity.
In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.
线粒体基因组中的一个点突变已被确定为糖尿病和耳聋的病因。我们报告了两个家系，其线粒体DNA（mtDNA）的亮氨酸转运RNA（UUR）基因的第3243位核苷酸发生了A到G的转换，并将研究重点放在该异常的其他定位上，特别是肌肉和视网膜。
通过侵入性和非侵入性方法对先证者的肌肉定位进行了研究，包括肌肉活检（评估与血细胞相比突变mtDNA的比例、测量呼吸链复合物活性以及组织学和组织化学方面）和31P核磁共振（NMR）光谱。对5名受试者进行了视网膜的眼科和血管造影检查、视网膜电图和视觉诱发电位检查。
这种先前在患有线粒体肌病、脑病、乳酸性酸中毒和卒中样发作（MELAS）的患者中描述过的突变，在肌肉中的表达比有核血细胞中更丰富。血细胞中的这种低表达可能会妨碍一些患者的诊断。此外，尽管临床表现不佳，但发现肌肉受到的影响很大。在肌肉活检中观察到破碎红纤维和营养不良的线粒体。组织化学分析显示呼吸链复合物的活性降低，体内31P-NMR数据进一步证实了肌肉氧化过程的缺陷。运动诱导的乳酸生成增加。最后，在两个家族中均观察到非典型的“椒盐”样色素性视网膜病变，但对视力无影响。
在继发于mtDNA 3243突变的糖尿病中，亚临床肌肉和眼部病变很常见。这两个疾病部位可以通过简单方法轻松进行检查，有助于诊断这种新型糖尿病。
