Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy

Abstract

Six patients in two unrelated families from the eastern Arabian peninsula presented with childhood-onset progressive external ophthalmoplegia (PEO), mild facial and proximal limb weakness, and severe cardiomyopathy requiring cardiac transplantation. Muscle biopsies showed ragged-red and cytochrome c oxidase-negative fibers. The activities of several complexes in the electron-transport chain were decreased and Southern blot analysis showed multiple mtDNA deletions. The apparent autosomal-recessive inheritance and the association with cardiomyopathy distinguish this syndrome from autosomal-dominant PEO with multiple mtDNA deletions. The combination of autosomal-recessive PEO, cardiomyopathy, and multiple mtDNA deletions appears to be another disease due to a defect of communication between the nuclear and mitochondrial genomes.