6个线粒体tRNALeu(UUR)基因突变糖尿病家系临床分析

目的 研究中国大连地区糖尿病（DM）人群中线粒体tRNA^Leu(UUR）3243位点A→G突变糖尿病的发病率及临床特点。方法 按照ADA（1997）/WHO（1999）DM诊断标准，采用PCR-RFLP技术筛查了629例DM患者，并对其中无亲缘关系的基因诊断阳性者及其一级亲属进行了基因和临床分析。结果 从DM患者中共检出6例基因突变先证者，从其一级亲属16个中检出该基因突变者12例，其中6例为线粒体DM，1例为IGT。患者不肥胖，发病年龄轻，9例有母系遗传，11例存在不同的听力障碍，5例因口服降糖药继发性失效，最终需用胰岛素治疗。结论 大连地区人群线粒体3243点突变检出率是0.95%。此类DM患者的临床特点是发病年龄轻，不胖，母系遗传，耳聋发生率和使用胰岛素比率高等。

A clinical analysis of 6 pedigrees with mitochondrial tRNALeu(UUR)gene mutation diabetes mellitus

Objective To investigate the incidence and clinical characteristics of mitochondrial tRNA Leu(UUR) gene at nucleotide 3243 A to G mutation in diabetic patients in Dalian District of China. Methods According to ADA(1997)/WHO(1999) diagnostic criteria of diabetes mellitus (DM), 629 patients with DM were screened by polymerase chain reaction and restriction fragment lenghth polymorphism. Genetic and clinical analyses were performed in unrelated patients with the mutation in mtDNA and their family members. Results Six unrelated subjects (probands) with the mutation were detected. Then 6 diabetes patients and 1 IGT from the first degree relatives of these 6 probands were also identified being with the mutation, in which 11 patients are associated with sensory hearing loss and 5 patients requires insulin therapy due to secondary failure to oral hypoglycemic agents. All these patients had lower weight, were younger at diagnosis and most of them were maternally inherited. Conclusion The mutation at nucleotide 3243 in the mitochondrial tRNA Leu(UUR) gene is an important cause of diabetes in Dalian District of China. Compared with the DM patients without the mutation, the clinical characteristics associated with this mutation are young at onset, non obese, maternally inherited and deafness, et al.