Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax, University of Sfax, Sfax, Tunisia.
Human Molecular Genetics Laboratory, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia.
Mol Genet Genomic Med. 2020 Jul;8(7):e1292. doi: 10.1002/mgg3.1292. Epub 2020 May 11.
Mitochondrial diabetes (MD) is a rare monogenic form of diabetes and divided into type l and type 2. It is characterized by a strong familial clustering of diabetes with the presence of maternal transmission in conjunction with bilateral hearing impairment in most of the carriers. The most common form of MD is associated with the m.3243A>G mutation in the mitochondrial MT-TL1, but there are also association with a range of other point mutations, deletion, and depletion in mtDNA.
The mitochondrial genome anomalies were investigated in a family with clinical features of MD, which includes a proband presenting severe MD conditions including cardiomyopathy, retinopathy, and psychomotor retardation.
By investigating the patient's blood leukocytes and skeletal muscle, we identified the m.3243A>G mutation in heteroplasmic state. This mutation was absent in the rest of the family members. In addition, our analysis revealed in the proband a large mtDNA heteroplasmic deletion (~1 kb) and a reduction in mtDNA copy number.
Our study points out, for the first time, a severe phenotypic expression of the m.3243A>G point mutation in association with mtDNA deletion and depletion in MD.
线粒体糖尿病（MD）是一种罕见的单基因糖尿病形式，分为 1 型和 2 型。其特征是糖尿病具有强烈的家族聚集性，大多数携带者存在母系遗传，并伴有双侧听力损失。最常见的 MD 形式与线粒体 MT-TL1 中的 m.3243A>G 突变相关，但也与一系列其他点突变、缺失和 mtDNA 耗竭相关。
对具有 MD 临床特征的家族进行了线粒体基因组异常调查，该家族包括一名表现出严重 MD 病症的先证者，包括心肌病、视网膜病变和精神运动迟缓。
通过对患者的血液白细胞和骨骼肌进行研究，我们发现存在异质型 m.3243A>G 突变。该突变在其余家族成员中不存在。此外，我们的分析还揭示了先证者存在大量 mtDNA 异质型缺失（~1kb）和 mtDNA 拷贝数减少。
我们的研究首次指出，m.3243A>G 点突变与 MD 中的 mtDNA 缺失和耗竭相关，表现出严重的表型表达。
