Abstract
In this part of a series on founder mutations in the Netherlands, we review a Dutch family carrying the SCN5a 1795insD mutation. We describe the advances in our understanding of the premature sudden cardiac deaths that have accompanied this family in the past centuries. The mutation carriers show a unique overlap of long-QT syndrome (type 3), Brugada syndrome and progressive cardiac conduction defects attributed to a single mutation in the cardiac sodium channel gene SCN5a. It is at present one of the largest and best-described families worldwide and we have learned immensely from the mouse strains with the murine homologue of the SCN5a 1795insD mutation (SCN5a 1798insD). From the studies currently performed we are about to obtain new insights into the phenotypic variability in this monogenic arrhythmia syndrome, and this might also be relevant for other arrhythmia syndromes and the general population. (Neth Heart J 2009;17:422–8.)
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Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Department of Clinical Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Department of Paediatrics, Division of Paediatric Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Clinical Genetics, Academic Hospital Maastricht, University of Maastricht, Maastricht, the Netherlands
Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, and Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
M.P. van den Berg Department of Cardiology, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
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Postema, P.G., Van den Berg, M.P., Van Tintelen, J.P. et al. Founder mutations in the Netherlands. NHJL 17, 422–428 (2009). https://doi.org/10.1007/BF03086296
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DOI: https://doi.org/10.1007/BF03086296