Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers.

Autor:	Claes GR; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands lieve.claes@mumc.nl., van Tienen FH; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Lindsey P; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Krapels IP; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Helderman-van den Enden AT; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Hoos MB; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Barrois YE; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Janssen JW; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands., Paulussen AD; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands., Sels JW; Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Intensive Care, Maastricht University Medical Centre, Maastricht, The Netherlands., Kuijpers SH; Department of Cardiology, Máxima Medical Centre, Eindhoven, The Netherlands., van Tintelen JP; Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands., van den Berg MP; Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands., Heesen WF; Department of Cardiology, VieCuri Medical Centre, Venlo, The Netherlands., Garcia-Pavia P; Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain., Perrot A; Charité-Universitätsmedizin Berlin, Experimental & Clinical Research Centre, A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrück Centre for Molecular Medicine, Berlin, Germany., Christiaans I; Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands., Salemink S; Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands., Marcelis CL; Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands., Smeets HJ; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands., Brunner HG; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands., Volders PG; Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands., van den Wijngaard A; Department of Clinical Genetics, Unit Clinical Genomics, Maastricht University Medical Centre, P.O. Box 5800, 6229 GR Maastricht, The Netherlands School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands.
Jazyk:	angličtina
Zdroj:	European heart journal [Eur Heart J] 2016 Jun 14; Vol. 37 (23), pp. 1815-22. Date of Electronic Publication: 2015 Oct 24.
DOI:	10.1093/eurheartj/ehv522
Abstrakt:	Aims: Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding in genotype-phenotype correlations in HCM, particularly the contribution of an MYL2 founder mutation and risk factors to left ventricular hypertrophic remodelling. Methods and Results: We analysed 14 HCM families of whom 38 family members share the MYL2 c.64G > A [p.(Glu22Lys)] mutation and a common founder haplotype. In this unique cohort, we investigated factors influencing phenotypic outcome in addition to the primary mutation. The mutation alone showed benign disease manifestation with low penetrance. The co-presence of additional risk factors for hypertrophy such as hypertension, obesity, or other sarcomeric gene mutation increased disease penetrance substantially and caused HCM in 89% of MYL2 mutation carriers (P = 0.0005). The most prominent risk factor was hypertension, observed in 71% of mutation carriers with HCM and an additional risk factor. Conclusion: The MYL2 mutation c.64G > A on its own is incapable of triggering clinical HCM in most carriers. However, the presence of an additional risk factor for hypertrophy, particularly hypertension, adds to the development of HCM. Early diagnosis of risk factors is important for early treatment of MYL2 mutation carriers and close monitoring should be guaranteed in this case. Our findings also suggest that the presence of hypertension or another risk factor for hypertrophy should not be an exclusion criterion for genetic studies. (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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