title: Sodium channelopathies: do we really understand what's going on?
abstract: Long-QT syndrome, Brugada syndrome, and conduction disease may be caused by mutations in the cardiac sodium channel gene SCN5A, and from the ECG one can already presume either a gain- or a loss-of-function defect. We describe a family harboring 2 SCN5A mutations: the ΔKPQ mutation, the "classical" gain-of-function mutation associated with Long-QT syndrome, and the I1660V mutation, a loss-of-function mutation associated with Brugada syndrome. However, we were surprised by the result of genetic testing in this family. One son who carried the ΔKPQ mutation but not the I1660V mutation did not show the expected Long-QT phenotype but, unexpectedly, showed a conduction disease/Brugada phenotype.
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Postema
authors.forename: Arend
authors.initials: A
authors.lastname: Mosterd
authors.forename: Nynke
authors.initials: N
authors.lastname: Hofman
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000368:Aged; D053840:Brugada Syndrome / Q000175:diagnosis* / Q000235:genetics*; D003937:Diagnosis, Differential; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels