线粒体tRNALeu(UUR)基因nt3243A→G突变糖尿病临床特点分析

目的 了解线粒体tRNALeu(UUR)基因nt3243A→G突变在上海及江浙地区家族性糖尿病人群中的发生率及其临床特点.方法 应用聚合酶链反应-限制性片段长度多态结合直接测序方法对随机抽取的无亲缘关系的770个糖尿病家系的先证者进行线粒体tRNA<'Leu(UUR)>基因nt3243A→G突变的筛查,并进一步对阳性先证者家系进行家系遗传学及临床特点分析.结果 在770个糖尿病先证者中发现13例(1.69%)nt3243A→G突变.13个先证者家系的一级亲属中共检出32例3243突变携带者,其中24例为糖尿病,8例糖耐量正常,17例伴不同程度听力减退.24例糖尿病患者多呈消瘦体型,有18例呈典型母系遗传,13例伴胰岛素抵抗,15例伴听力障碍,14例应用胰岛素治疗.结论 上海及江浙地区家族性糖尿病人群线粒体3243点突变检出率是1.69%,线粒体糖尿病患者的临床特点是:(1)多数呈母系遗传,少数可为散发;(2)多于45岁以前发病;(3)体型多偏瘦;(4)胰岛β细胞分泌功能明显降低,部分患者同时伴有胰岛素抵抗;(5)多数患者伴神经性听力障碍或神经性耳聋.

Prevalence and clinical characteristics of the mitochondriai tRNALeu(UUR) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population

Objective To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Methods The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the prohands and their family members. Results Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index(BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents. Conclusion The mutation of mt3243 A to G in the mitochondrial tRNALeu(UUR) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower isletβcell function, and some have insulin resistance.