6例母系遗传糖尿病患者线粒体基因突变分析

发布时间：2018-06-04 04:24

  本文选题：糖尿病 + 线粒体　； 参考：《济南大学》2017年硕士论文

【摘要】：目的线粒体糖尿病(mitochondrial diabetes mellitus,MDM)是糖尿病的一种特殊类型,由线粒体基因突变引起,属于β细胞遗传缺陷性疾病,国内外已报道的相关线粒体基因(Mitochondrial DNA,mt DNA)突变位点达数十种[1],其中位于t RNALeu(UUR)基因上的A3243G突变是MDM最常见的致病性突变,特点为母系遗传糖尿病伴神经性耳聋,即MIDD(maternally inherited diabetes and deafness syndrome)。线粒体基因突变具有高度多态性,使个体带有一定遗传易感性及临床异质性,即携带同一突变的个体表现出不同类型、不同程度的临床表型。本研究对6例2型糖尿病母系遗传患者进行线粒体基因分析,探讨线粒体基因突变与患者糖尿病临床表型之间的关系。方法从山东内分泌与代谢病医院临床资料库中收集4例母系遗传伴耳聋的2型糖尿病患者和2例母系遗传无耳聋的糖尿病患者进行研究。受试者行空腹血糖、糖化血红蛋白、胰岛素功能试验等检测。体格检查包括:身高、体重,计算体重指数。对受试者家族史进行初步调查。抽取受试者外周血进行基因提取,用聚合酶链反应(Polymerase chain reaction,PCR)对线粒体3069-3842片段进行直接测序,有突变或有意义者行线粒体全基因(除D环区外)测序,以明确是否有线粒体基因突变。结果6名受试者在线粒体3069-3842片段中,有1例受试者发现T3535C同义突变,由稀有密码子突变为常用密码子。对此患者进一步行线粒体全基因测序(除D环区外),发现G9053A、T10609C、C10920T、G13759A、G13928C、A15326G共6个错义突变,2个非编码区突变,13个同义突变,其中在线粒体还原型辅酶Ⅰ(NADH)脱氢酶基因ND1上连续有2个T3535C、C3970T突变导致密码子改变。结论本研究共发现了6个线粒体错义突变,其中C10920T(P→L)突变与患者母系遗传糖尿病伴耳聋临床表型相关。
[Abstract]:Objective Mitochondrial diabetes mellitusus (MDM) is a special type of diabetes mellitus, which is caused by mitochondrial gene mutation and belongs to 尾 cell genetic defect disease. There are dozens of mtDNA mutation sites reported at home and abroad, in which A3243G mutation located on t RNALeuuuru) gene is the most common pathogenicity mutation of MDM, characterized by maternal genetic diabetes with neurogenic deafness, I. e., MIDD(maternally inherited diabetes and deafness syndromeis. Mitochondrial gene mutation is highly polymorphic, which makes individuals with certain genetic susceptibility and clinical heterogeneity, that is, individuals with the same mutation show different types and different degrees of clinical phenotype. This study investigated the relationship between mitochondrial gene mutation and clinical phenotype in 6 patients with type 2 diabetes mellitus. Methods four cases of type 2 diabetes with maternal inheritance and deafness and two cases of non-deafness with maternal inheritance were collected from clinical database of Shandong Endocrine and Metabolism Hospital. Fasting blood glucose, glycosylated hemoglobin and insulin function test were measured. Physical examination includes height, weight, and calculation of body mass index. The family history of the subjects was investigated. The gene was extracted from the peripheral blood of the subjects. The mitochondrial 3069-3842 fragment was directly sequenced by polymerase chain reaction (PCR). The whole mitochondrial gene (except D loop) was sequenced in those with mutation or significance. To determine if there is a mitochondrial gene mutation. Results one of the 6 subjects found T3535C synonymous mutation in the mitochondrial 3069-3842 fragment, which changed from rare codon to common codon. The patients were further sequenced by mitochondrial gene sequencing (except for D loop region, 6 missense mutations, 2 non-coding region mutations, 13 synonymous mutations) were found in G9053AX T10609CnC10609C10920TG13759AG13928CnA15326G. In the mitochondrial reductive coenzyme 鈪，

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