Author + information
- T. Novotny1,
- I. Synkova2,
- I. Andrsova1,
- R. Gaillyova2,
- I. Valaskova2,
- P. Vit3,
- T. Chlupova1,
- M. Bebarova4,
- O. Svecova4,
- J. Hosek5 and
- J. Spinar1
- 1Department of Internal Medicine and Cardiology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 2Department of Medical Genetics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 3Department of Paediatrics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 4Department of Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
- 5Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Veterinary and Pharmaceutical University Brno, Brno, Czech Republic
Mutations in up to 15 genes have been associated with long QT syndrome (LQTS), most encoding for subunits of cardiac ionic channels. In majority of cases, each family has its “own” mutation.
Individuals with suspected LQTS are regularly investigated in University Hospital Brno, all of them undergo clinical examination including bicycle ergometry and genetic consult. In patients with clinically confirmed diagnosis of LQTS, mutation analysis of LQT-related genes (mostly KCNQ1, KCNH2, SCN5A) is performed. Previously, single strand conformational polymorphism methods and automatic sequencing were utilized, recently, we have started to use next generation sequencing.
KCNQ1 gene mutations were found in 30 unrelated families (88 individuals, 52 mutation-carriers) with clinical diagnosis of LQTS during years 2000-2016. In 5 families (16%) the same T309I variant was the causative mutation segregating with pathological LQTS phenotype. According to preliminary biophysical data, the mutation seems to generate non-functional channels.
High incidence of T309I mutation in KCNQ1 gene supports a hypothesis that this might be a founder mutation in our region. Further pedigree extension and geographic localization of ancestor origin is ongoing.