Open AccessMutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of Long QT syndrome
Author(s) -
Martina Raudenská,
Alexandra Bittnerová,
Tomáš Novotný,
Alena Floriánová,
Karel Chroust,
Renata Gaillyová,
Bořivoj Semrád,
Jitka Kadlecová,
Martina Šišáková,
Ondřej Toman,
Jindřich Špinar
Publication year - 2008
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931184
Subject(s) - genetics , candidate gene , long qt syndrome , biology , torsades de pointes , gene , mutation , qt interval , medicine
The long QT syndrome (LQTS) is a monogenic disordercharacterized by prolongation of the QT interval onelectrocardiogram and syncope or sudden death caused bypolymorphic ventricular tachycardia (torsades de pointes). Ingeneral, mutations in cardiac ion channel genes (KCNQ1, KCNH2,SCN5A, KCNE1, KCNE2) have been identified as a cause forLQTS. About 50-60 % of LQTS patients have an identifiable LQTScausing mutation in one of mentioned genes. In a group of 12LQTS patients with no identified mutations in these genes wehave tested a hypothesis that other candidate genes could beinvolved in LQTS pathophysiology. SCN1B and KCND3 genesencode ion channel proteins, ANK2 gene encodes cytoskeletalprotein interacting with ion channels. To screen coding regions ofgenes SCN1B, KCND3, and 10 exons of ANK2 following methodswere used: PCR, SSCP, and DNA sequencing. Five polymorphismswere found in screened candidate genes, 2 polymorphisms inKCND3 and 3 in SCN1B. None of found polymorphisms hascoding effect nor is located close to splice sites or has anysimilarity to known splicing enhancer motifs. PolymorphismG246T in SCN1B is a novel one. No mutation directly causingLQTS was found. Molecular mechanism of LQTS genesis in thesepatients remains unclear.