Objective: To investigate the mutations of mitochondrial genome in a pedigree with suspected maternally inherited diabetes and deafness and to explore the correlations between the mutations and clinical features.
Methods: Genomic DNA was isolated from blood leucocytes of each member of the pedigree. The mitochondrial genome was amplified with 24-pair primers that could cover the entire mitochondrial DNA. Direct sequencing of PCR products was used to identify any mitochondrial DNA mutations.
Results: Family members on the maternal side all harbored the tRNALeu(UUR) A3243G mutation. The paternal side family members did not have the mutation. The age-of-onset of diabetes of the 4 maternal side family members was 15, 41, 44, and 65 years old, and their corresponding heteroplasmy level of the mutation was 34.5%, 14.9%, 14.6%, and 5.9%, respectively. The age-of-onset of diabetes and heteroplasmy level of A3243G mutation were negatively correlated with a correlation coefficient of -0.980 (P = 0.02). Meanwhile, patient with high heteroplasmy level of A3243G mutation had relatively low severity of disease. Moreover, 6 reported polymorphisms and 2 new variants were found.
Conclusions: The main cause of diabetes in this pedigree is the tRNALeu(UUR) A3243G mutation. However, other gene variants may contribute to its pathogenicity. The heteroplasmy level of the tRNALeu(UUR) A3243G mutation is positively associated with earlier age-of-onset and increasing severity of diabetes.