本文選題：糖尿病 + 線粒體�。� 參考：《濟(jì)南大學(xué)》2017年碩士論文

【摘要】：目的線粒體糖尿病(mitochondrial diabetes mellitus,MDM)是糖尿病的一種特殊類型,由線粒體基因突變引起,屬于β細(xì)胞遺傳缺陷性疾病,國(guó)內(nèi)外已報(bào)道的相關(guān)線粒體基因(Mitochondrial DNA,mt DNA)突變位點(diǎn)達(dá)數(shù)十種[1],其中位于t RNALeu(UUR)基因上的A3243G突變是MDM最常見(jiàn)的致病性突變,特點(diǎn)為母系遺傳糖尿病伴神經(jīng)性耳聾,即MIDD(maternally inherited diabetes and deafness syndrome)。線粒體基因突變具有高度多態(tài)性,使個(gè)體帶有一定遺傳易感性及臨床異質(zhì)性,即攜帶同一突變的個(gè)體表現(xiàn)出不同類型、不同程度的臨床表型。本研究對(duì)6例2型糖尿病母系遺傳患者進(jìn)行線粒體基因分析,探討線粒體基因突變與患者糖尿病臨床表型之間的關(guān)系。方法從山東內(nèi)分泌與代謝病醫(yī)院臨床資料庫(kù)中收集4例母系遺傳伴耳聾的2型糖尿病患者和2例母系遺傳無(wú)耳聾的糖尿病患者進(jìn)行研究。受試者行空腹血糖、糖化血紅蛋白、胰島素功能試驗(yàn)等檢測(cè)。體格檢查包括:身高、體重,計(jì)算體重指數(shù)。對(duì)受試者家族史進(jìn)行初步調(diào)查。抽取受試者外周血進(jìn)行基因提取,用聚合酶鏈反應(yīng)(Polymerase chain reaction,PCR)對(duì)線粒體3069-3842片段進(jìn)行直接測(cè)序,有突變或有意義者行線粒體全基因(除D環(huán)區(qū)外)測(cè)序,以明確是否有線粒體基因突變。結(jié)果6名受試者在線粒體3069-3842片段中,有1例受試者發(fā)現(xiàn)T3535C同義突變,由稀有密碼子突變?yōu)槌Ｓ妹艽a子。對(duì)此患者進(jìn)一步行線粒體全基因測(cè)序(除D環(huán)區(qū)外),發(fā)現(xiàn)G9053A、T10609C、C10920T、G13759A、G13928C、A15326G共6個(gè)錯(cuò)義突變,2個(gè)非編碼區(qū)突變,13個(gè)同義突變,其中在線粒體還原型輔酶Ⅰ(NADH)脫氫酶基因ND1上連續(xù)有2個(gè)T3535C、C3970T突變導(dǎo)致密碼子改變。結(jié)論本研究共發(fā)現(xiàn)了6個(gè)線粒體錯(cuò)義突變,其中C10920T(P→L)突變與患者母系遺傳糖尿病伴耳聾臨床表型相關(guān)。
[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，

本文編號(hào)：1975905