Kishimoto M, Hashiramoto M, Araki S, Ishida Y, Kazumi T, Kanda E, Kasuga M
Second Department of Internal Medicine, Kobe University, School of Medicine, Japan.
Diabetologia. 1995 Feb;38(2):193-200. doi: 10.1007/BF00400094.
We screened 214 Japanese NIDDM (non-insulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA(Leu(UUR)) gene using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA(Leu(UUR)) gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alpha-cell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes.
我们使用聚合酶链反应-限制性片段长度多态性和直接测序技术，对214名有糖尿病家族史的日本非胰岛素依赖型糖尿病（NIDDM）患者的线粒体tRNA（Leu（UUR））基因突变情况进行了筛查。6名患者被确定在线粒体tRNA（Leu（UUR））基因的3243位存在A到G的转换（3243突变），但未检测到患者在线粒体tRNA（Leu（UUR））基因的3271位有T到C的转换。这两种突变在85名健康对照者中均未出现。结果显示，6例中有5例患者的母亲也患有糖尿病。在这6例受影响的患者中，3243突变表现出不同的表型，如多器官受累程度、家族内和家族间疾病特征的差异以及线粒体肌病、脑病、乳酸酸中毒和卒中样发作（MELAS）表型的受累程度。内分泌检查发现，那些具有3243突变的糖尿病患者不仅存在β细胞功能障碍，还存在α细胞功能缺陷，这被认为是3243突变糖尿病的特征。与50名选定的无3243突变的糖尿病对照患者相比，后者的母亲而非父亲患有糖尿病，经统计学分析确定，具有3243突变的患者具有以下临床特征：1）糖尿病发病年龄较低；2）体型偏瘦；3）与对照患者相比，他们更有可能接受胰岛素治疗。我们认为，具有3243突变的糖尿病具有与常见糖尿病形式不同的表型。
