AIMS—To clarify the phenotype-genotype relation associated with the A3243G mitochondrial DNA mutation.
METHODS—Five unrelated probands harbouring the A3243G mutation but presenting different clinical phenotype were analysed. Probands include Leigh syndrome (LS³²⁴³), mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS³²⁴³), progressive external ophthalmoplegia (PEO³²⁴³), and mitochondrial diabetes mellitus (MDM³²⁴³). Extensive clinical, histological, biochemical, and molecular genetic studies were performed on five families.
RESULTS—All patients showed ragged red fibres (RRF), and focal cytochrome c oxidase (COX) deficiency except for the patient with MDM³²⁴³. The mutation load was highest in the proband with LS³²⁴³ (>90%), who also presented the highest proportion of RRF (68%) and COX negative fibres (10%), and severe complex I plus IV deficiency. These proportions were lower in the probands with PEO³²⁴³ and with MDM³²⁴³.
CONCLUSION—The most severe clinical phenotype, LS³²⁴³, was associated with the highest proportion of the A3243G mutation as well as the most prominent histological and biochemical abnormalities.