title: A mitochondrial DNA mutation cosegregates with the pathophysiological U wave.
abstract: In a family with long QT syndrome (LQT2), some individuals who did not harbor the HERG mutation had a prolonged QTU interval on electrocardiograms after 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 (mutation at 3394) showed significantly reduced NADH-CoQ reductase (complex I) activity and O2 consumption to normal levels. These inhibitory effects on respiratory function may result in the depletion of ATP and could possibly produce an increase in Ca2+ concentration in cytosol, and it may lead to the prolongation of the QTU intervals on electrocardiograms. Therefore, we stated that the 3394 mutation in the ND1 gene is pathogenic and could be the cause of prolongation of the QTU intervals or modification of the phenotypes of not only congenital but also so-called "acquired drug-induced long QT syndrome."
authors: Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Shinjuku-ku, 1628666, USA. rumiko@imcir.twmu.ac.jp
authors: R
authors: R
authors: Matsuoka
authors: M
authors: M
authors: Furutani
authors: J
authors: J
authors: Hayashi
authors: K
authors: K
authors: Isobe
authors: K
authors: K
authors: Akimoto
authors: T
authors: T
authors: Shibata
authors: S
authors: S
authors: Imamura
authors: M
authors: M
authors: Tatsuguchi
authors: Y
authors: Y
authors: Furutani
authors: A
authors: A
authors: Takao
authors: S
authors: S
authors: Ohnishi
authors: H
authors: H
authors: Kasanuki
authors: K
authors: K
authors: Momma
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels; D005080:Exercise Test; D005260:Female; D005333:Fetus; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D008133:Long QT Syndrome / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009245:NADH Dehydrogenase; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012119:Respiration; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: D002118:Calcium; D027682:Cation Transport Proteins; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV; D051638:Ether-A-Go-Go Potassium Channels; D019476:Insect Proteins; D009245:NADH Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D010100:Oxygen; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C072312:ERG protein, human; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C515075:NADH dehydrogenase subunit 1, human