BACKGROUND: Long QT syndrome (LQTS) is among arrhythmia disorders of the heart that causes sudden cardiac death in young individuals. As yet, most of investigations have focused on nuclear genome for finding genetic defects in this disorder, but some of the cases with LQTS cannot be explained by mutations of identified genes. On the other hand, it has been reported that the activity of ion channels in cardiomyocytes is sensitive to ATP level. It prompted us to focus on the mitochondrial DNA and monitor the point mutations of genome which are probably the cause of respiratory chain defects and reduced ATP generation. METHODS: We searched about 55% of the mitochondrial DNA (mtDNA) by temporal temperature gradient gel electrophoresis (TTGE), and DNA fragments showing abnormal banding patterns were sequenced for identification of exact mutations. RESULTS: In 39 patients (33 familial and 6 sporadic cases), for the first time, we detected 35 mtDNA mutations in which 8 were novel (23%) and 27 (77%) have been reported in other mitochondrial diseases. Our results showed that these mutations in LQTS patients were higher than those in normal controls (P<.0001), and the number of mutations in LQTS patients with syncope is higher than in patients without syncope (P<.001). CONCLUSIONS: As the mitochondrion's ATP synthesis is important in heart, it is possible that mutations and their accumulation in mtDNA could constitute a predisposing factor that in combination with environmental factors may trigger the syncope in patients with LQTS.
BACKGROUND:Long QT syndrome (LQTS) is among arrhythmia disorders of the heart that causes sudden cardiac death in young individuals. As yet, most of investigations have focused on nuclear genome for finding genetic defects in this disorder, but some of the cases with LQTS cannot be explained by mutations of identified genes. On the other hand, it has been reported that the activity of ion channels in cardiomyocytes is sensitive to ATP level. It prompted us to focus on the mitochondrial DNA and monitor the point mutations of genome which are probably the cause of respiratory chain defects and reduced ATP generation. METHODS: We searched about 55% of the mitochondrial DNA (mtDNA) by temporal temperature gradient gel electrophoresis (TTGE), and DNA fragments showing abnormal banding patterns were sequenced for identification of exact mutations. RESULTS: In 39 patients (33 familial and 6 sporadic cases), for the first time, we detected 35 mtDNA mutations in which 8 were novel (23%) and 27 (77%) have been reported in other mitochondrial diseases. Our results showed that these mutations in LQTS patients were higher than those in normal controls (P<.0001), and the number of mutations in LQTS patients with syncope is higher than in patients without syncope (P<.001). CONCLUSIONS: As the mitochondrion's ATP synthesis is important in heart, it is possible that mutations and their accumulation in mtDNA could constitute a predisposing factor that in combination with environmental factors may trigger the syncope in patients with LQTS.