A mitochondrial DNA mutation cosegregates with the pathophysiological U wave

In a family with long QT syndrome (LQT2), some individuals who did not harb or the HERB mutation had a prolonged QTU interval on electrocardiograms aft er exercise. It may be determined or modified by other gene(s) or factor(s) . The sequence analysis of mtDNA in these individuals of this family showed a candidate pathogenic mutation at 3394 in the ND1 gene. The cybrids (muta tion at 3394) showed significantly reduced NADH-CoQ reductase (complex I) a ctivity and O-2 consumption to normal levels. These inhibitory effects on r espiratory function may result in the depletion of ATP and could possibly p roduce an increase in Ca2+ concentration in cytosol, and it may lead to the prolongation of the QTU intervals on electrocardiograms. Therefore, we sta ted that the 3394 mutation in the ND1 gene is pathogenic and could be the c ause of prolongation of the QTU intervals or modification of the phenotypes of not only congenital but also so-called "acquired drug-induced long QT s yndrome." (C) 1999 Academic Press.