Objectives: To define the molecular genetic basis of the MELAS phenotype in five patients without any known mutation of mitochondrial DNA.
Methods: Systematic automated mitochondrial DNA sequencing of all mitochondrial transfer RNA and cytochrome c oxidase genes was undertaken in five patients who had the MELAS phenotype.
Results: A novel heteroplasmic mitochondrial DNA mutation was identified in the transfer RNA gene for phenylalanine in one case (patient 3). This mutation was not detected in the patient's blood or in her mother's blood. No pathogenic mutations were identified in the other four patients.
Conclusions: This is the first point mutation in the transfer RNA gene for phenylalanine to be associated with MELAS. The absence of mutations in the remaining four patients suggests that there is further genetic heterogeneity associated with this mitochondrial phenotype.