Development of a Long QT-Syndrome mutation detection method.

Abstract: Sudden cardiac death (SCD) especially in younger adults with no previous symptoms is a challenging problem in forensic diagnostics, occurring with an incidence of about 80,000 per year in Germany. Long QT-Syndrome (LQTS) and other cardiac disorders associated with abnormality of cardiac rhythm triggered by mutations of cardiac ion channels have to consider if no cause of death is detectable during autopsy. A molecular genetic screening can help to ensure. Meanwhile twelve genes are known in which more than 700 different mutations are associated with LQTS. The three major LQTS-susceptibility genes are KCNQ1, KCNH2 and SCN5A. They are responsible for 75% of all congenital LQTS cases. We developed a rapid, sensitive and reasonable method for the simultaneously screening of the most common LQTS mutations, focused on these three genes. Using the SNaPshot^® minisequencing primer extension assay a total of 91 Single-Nucleotide Polymorphisms (SNPs) were examined in six multiplex assays. The data suggest that this technique is applicable, solid, flexible and a good alternative to complete sequencing. [Copyright &y& Elsevier]