The first linkage studies in families with inherited arrhyth-mogenic disorders, among which was the long-QT syndrome (LQTS), fully relied upon good clinical definition of the phe-notype and correct classification of affected and unaffected individuals as being imperative to find linkage and, therefore, the causative mutations. These studies successfully showed that mutations in genes coding for ion channels were responsible for genetically determined rhythm disorders such as LQTS. Since then, hundreds of mutations in 13 genes have been described to associate with LQTS. Sequencing of candidate genes has become a routine procedure in the diagnosis of LQTS and mutations in the 3 major LQT susceptibility genes KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3) are found in >90% of successfully genotyped congenital LQTS cases.
展开▼
