HIGH PROPORTIONS OF MTDNA DUPLICATIONS IN PATIENTS WITH KEARNS-SAYRE-SYNDROME OCCUR IN THE HEART

Kearns-Sayre syndrome (KSS) is a sporadic multisystem mitochondrial di sorder-characterized by progressive external ophthalmoplegia, pigmenta ry retinopathy, onset before age 20, and severe cardiac conduction def ects that can lead to death, KSS patients harbor partial deletions of mitochondrial DNA (Delta-mtDNA), sometimes associated with the corresp onding mtDNA duplication (dup-mtDNA), As reports on the distribution o f dup-mtDNAs among KSS tissues are scarce, we searched for the presenc e of dup-mtDNAs in different autopsy tissues of two such patients, one of whom carried the so-called ''common deletion.'' Using a newly deve loped long polymerase chain reaction (PCR) protocol in conjunction wit h Southern blot analyses, we found dup-mtDNAs in most of the examined tissues from both patients, The proportion of dup-mtDNA in these tissu es was much lower than the proportion of Delta-mtDNA, with one notable exception: in both patients, we found an unusually high level of dup- mtDNA in the heart, These data suggest that dup-mtDNAs may be more sta ble in heart tissue of KSS patients than in other long-lived postmitot ic tissues, (C) 1997 Wiley-Liss, Inc.