Gepubliceerd in:
2014 | OriginalPaper | Hoofdstuk
9. Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D*
Auteurs : K. Y. van Spaendonck-Zwarts, A. J. van der Kooi, M. P. van den Berg, E. F. Ippel, L. G. Boven, W.-C. Yee, A. van den Wijngaard, E. Brusse, J. E. Hoogendijk, P. A. Doevendans, M. de Visser, J. D. H. Jongbloed, J. P. van Tintelen
Gepubliceerd in: Founder mutations in inherited cardiac diseases in the Netherlands
Uitgeverij: Bohn Stafleu van Loghum
Samenvatting
Background
Desmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES). We describe new families carrying the p.S13F or p.N342D DES mutations, the cardiac phenotype of all carriers, and the founder effects.
Methods
We collected the clinical details of all carriers of p.S13F or p.N342D. The founder effects were studied using genealogy and haplotype analysis.
Results
We identified three new index patients carrying the p.S13F mutation and two new families carrying the p.N342D mutation. In total, we summarised the clinical details of 39 p.S13F carriers (eight index patients) and of 21 p.N342D carriers (three index patients). The cardiac phenotype of p.S13F carriers is fully penetrant and severe, characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement. Although muscle weakness is a prominent and presenting symptom in p.N342D carriers, their cardiac phenotype is similar to that of p.S13F carriers. The founder effects of p.S13F and p.N342D were demonstrated by genealogy and haplotype analysis.
Conclusion
DRM may occur as an apparently isolated cardiological disorder. The cardiac phenotypes of the DES founder mutations p.S13F and p.N342D are characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement.