Mapping of heteroplasmic mitochondrial DNA deletions in Kearns-Sayre syndrome

Kearns-Sayre syndrome (KSS) is a progressive neuromuscular disease characterised by ophtalmoplegia, cardiac bloc branch, pigmentary retinopathy associated with abnormal mitochondrial function. We have studied the mitochondrial DNA organization of patients presenting KSS and have found large deletions ranging from 3 to 8.5 kilobase pairs. DNA molecules containing deletion are accompanied by the presence of the normal sized mtDNA molecule forming heteroplasmic genomes. The deletions always map in the region which is potentially single stranded during mitochondrial DNA replication. The deletions differ in length and position between individuals but are similar within the different tissues of an individual suggesting that they arise during or before embryogenesis.