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

Abstract

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.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.

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.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.

Conclusion

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.

Abstract

Identification of de novo m.3243A>G mutation in a patient with complicated mitochondrial diabetes. This known pathogenic mutation is present with a high heteroplasmic rate and for the first time, it is associated with a large mitochondrial deletion (~1.0kb) and depletion of the mitochondrial content. So, we discuss here the correlation between these mitochondrial alterations and the severity of mitochondrial diabetes.