Mitochondrial-DNA nucleotides G4298A and T10010C as pathogenic mutations: The confirmation in two new cases

Mitochondrial encephalomyopathies are highly variable clinically and at the genetic level. In practice, when the mitochondrial DNA (mtDNA) of any mitochondrial-patient is sequenced, a very high number of variations are noted. The vast majority of these differences are simply polymorphisms, that is, non-pathologic, homoplasmic sequence variations; however, when a heteroplasmic variant is detected (co-existence of two different populations in the same tissue) this is clinically significant. We identified two different heteroplasmic mutations in the mtDNA of two subjects: G4298A in the tRNA^Ala (Alanine) gene and T10010C in the tRNA^Gly (Glycine), both of which have been reported previously. This work confirms the pathogenicity of these mutations and helps define the correlation between genotype and phenotype.