The first concurrent detection of mitochondrial DNA m.3243AG mutation, deletion, and depletion in a family with mitochondrial diabetes

摘要

Background 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.3243AG mutation in the mitochondrial MT‐TL1, but there are also association with a range of other point mutations, deletion, and depletion in mtDNA. Methods 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. Results By investigating the patient's blood leukocytes and skeletal muscle, we identified the m.3243AG 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. Conclusion Our study points out, for the first time, a severe phenotypic expression of the m.3243AG point mutation in association with mtDNA deletion and depletion in MD.