FINE MAPPING OF RANDOMLY DISTRIBUTED MULTIPLE DELETIONS OF MITOCHONDRIAL-DNA IN A CASE OF CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA

Multiple deletions of mitochondrial DNA have been detected by Southern blotting in the skeletal muscle of a 42-year-old woman with chronic p rogressive external ophthalmoplegia. A PCR method, using several combi nations of primers covering the whole mtDNA as well as sequence analys is, disclosed the wide spectrum of these multiple deletions differing in size, location and sequence at the breakpoint junction. Most involv ed the major region between the two replication origins. However, thre e deletions affected the minor region and lacked either the light stra nd origin of replication or the heavy strand promoter. These data sugg est an impairment of mtDNA replication leading to illegitimate recombi nation and extensive damage of mtDNA.