THE COMMON 4977-BASE-PAIR DELETION OF MITOCHONDRIAL-DNA PREFERENTIALLY ACCUMULATES IN THE CARDIAC CONDUCTION SYSTEM OF PATIENTS WITH KEARNS-SAYRE-SYNDROME

Previous studies of cytochrome c oxidase (complex IV of the respirator y chain) in the heart of a 26-year-old man with longstanding Kearns-Sa yre syndrome and fatal congestive cardiomyopathy had revealed the pres ence of randomly distributed enzyme-deficient cardiomyocytes, both in the contractile and the conducting myocardium. In the present study, t he conduction system of the heart was screened for the occurrence of t he common 4977 base pair deletion (8, 482-13, 459) of mitochondrial DN A (mtDNA) in formalin-fixed, paraffin-embedded tissue and compared wit h the contractile myocardium. Polymerase chain reaction analysis revea led that in the sinus node, the atrioventricular node, and the bundle branches, 35 to 40% of total mtDNA molecules harbored the common delet ion. In contrast, in the contractile myocardium, 10 to 20% of total mt DNA was deleted (P = .05). These results demonstrate that in Kearns-Sa yre syndrome, the conduction system of the heart preferentially accumu lates the common deletion. This finding might help to explain the high prevalence of cardiac dysrhythmias in this syndrome.