Recurrent and founder mutations in the Netherlands: the cardiac phenotype of founder mutations p.S13F and p.N342D

Autor: E. F. Ippel, A. J. van der Kooi, A. van den Wijngaard, Esther Brusse, J. P. van Tintelen, K. Y. van Spaendonck-Zwarts, M.P. van den Berg, Jessica E. Hoogendijk, Ludolf G. Boven, W. C. Yee, J. D. H. Jongbloed, Pieter A. Doevendans, M. de Visser
Přispěvatelé: Ethical, Legal, Social Issues in Genetics (ELSI), Cardiovascular Centre (CVC), Cell biology, Neurology, Pediatric Surgery, MUMC+: DA KG Lab Centraal Lab (9), Klinische Genetica, Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases, Human Genetics, Amsterdam Neuroscience, Other departments
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Netherlands Heart Journal, 20(5), 219-228. Bohn, Stafleu, Van Loghum
Netherlands Heart Journal
Netherlands Heart Journal, 20(5), 219-228. Bohn Stafleu van Loghum
Netherlands heart journal, 20(5), 219-228. Bohn Stafleu van Loghum
ISSN: 1876-6250
1568-5888
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s12471-011-0233-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
Externí odkaz: