Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene

Mitochondrial cytochrome b mutations have been reported to have a homogenous phenotype of pure exercise intolerance. We describe a novel mutation in the cytochrome b gene of mitochondrial DNA (A15579G) associated with a selective decrease of muscle complex III activity in a patient who, besides severe exercise intolerance, also has multisystem manifestations (deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, epilepsy). The point mutation is heteroplasmic in muscle (88%) and leukocytes (15%), and changes a highly conserved tyrosine to cysteine at amino acid position 278.