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Clinical phenotype of mitochondrial diabetes due to rare mitochondrial DNA mutations.
Annales d'Endocrinologie ( IF 2.9 ) Pub Date : 2020-04-28 , DOI: 10.1016/j.ando.2020.04.007
Anne-Gaëlle Decoux-Poullot 1 , Sylvie Bannwarth 2 , Vincent Procaccio 3 , Anne-Sophie Lebre 4 , Claude Jardel 5 , Bernard Vialettes 6 , Véronique Paquis-Flucklinger 2 , Nicolas Chevalier 7
Affiliation  

OBJECTIVE While the most frequent mutation responsible for mitochondrial diabetes is the point mutation m.3243 A>G of mitochondrial DNA (mtDNA), few data are available about the role of rare mtDNA mutations in the pathophysiology of diabetes. The main objective of our study was to describe the phenotypic characteristics of patients suffering from diabetes linked to rare mtDNA mutations. RESEARCH DESIGN AND METHODS We performed a post-hoc analysis of a prospective multicenter cohort of 743 patients with mitochondrial disorder (previously published by the French Network of Mitochondrial Diseases), associated to a literature review of the PubMed database from 1992 to May 2016. We extracted all reported patients with diabetes and identified rare mtDNA mutations and described their clinical and metabolic phenotypes. RESULTS The 50 identified patients (10 from the princeps study; 40 from the review of the literature) showed a heterogeneous metabolic phenotype in terms of age, symptoms prior to diagnosis, treatments, and associated clinical and biological signs. However, neurological symptoms were more frequent in case of rare mtDNA mutations compared to the classical m.3243 A>G mutation (P=0.024). In contrast, deafness (65% vs. 95%, P=3.7E-5), macular pattern dystrophy (20% vs. 86%, P=1.6E-10) and nephropathy (8% vs. 28%, P=0.018) were significantly less frequent than in case of the classical m.3243 A>G mutation. CONCLUSION Although no specific metabolic phenotype could be identified suggesting or eliminating implication of rare mtDNA mutations in diabetes, clinical phenotypes featured more frequent neurological signs.

中文翻译:

线粒体糖尿病的临床表型归因于罕见的线粒体DNA突变。

目的尽管线粒体糖尿病最常见的突变是线粒体DNA(mtDNA)的点突变m.3243 A> G,但很少有关于罕见mtDNA突变在糖尿病病理生理中的作用的数据。我们研究的主要目的是描述与罕见的mtDNA突变相关的糖尿病患者的表型特征。研究设计和方法我们对743名线粒体疾病患者(先前由法国线粒体疾病网络出版)的前瞻性多中心队列进行了事后分析,该研究与1992年至2016年5月PubMed数据库的文献综述相关。提取了所有报告的糖尿病患者并鉴定了罕见的mtDNA突变,并描述了他们的临床和代谢表型。结果根据年龄,诊断之前的症状,治疗以及相关的临床和生物学体征,经鉴定的50例患者(其中10例来自princeps研究; 40例来自文献综述)显示出异质代谢表型。但是,与经典的m.3243 A> G突变相比,在罕见的mtDNA突变的情况下,神经系统症状更为常见(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。文献综述中的40)在年龄,诊断之前的症状,治疗以及相关的临床和生物学体征方面显示出异质代谢表型。但是,与经典的m.3243 A> G突变相比,在罕见的mtDNA突变的情况下,神经系统症状更为常见(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。文献综述中的40)在年龄,诊断之前的症状,治疗以及相关的临床和生物学体征方面显示出异质代谢表型。但是,与经典的m.3243 A> G突变相比,在罕见的mtDNA突变的情况下,神经系统症状更为常见(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。诊断,治疗前的症状,以及相关的临床和生物学症状。但是,与经典的m.3243 A> G突变相比,在罕见的mtDNA突变的情况下,神经系统症状更为常见(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。诊断,治疗前的症状,以及相关的临床和生物学症状。但是,与经典的m.3243 A> G突变相比,在罕见的mtDNA突变的情况下,神经系统症状更为常见(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。3243A> G突变(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。3243A> G突变(P = 0.024)。相反,耳聋(65%比95%,P = 3.7E-5),黄斑型营养不良(20%比86%,P = 1.6E-10)和肾病(8%比28%,P = 0.018)的频率明显低于经典m.3243 A> G突变的频率。结论尽管无法鉴定出特定的代谢表型,提示或消除了糖尿病中罕见的mtDNA突变的影响,但临床表型具有更频繁的神经系统症状。
更新日期:2020-04-28
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