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

Item Type:Article
Title:Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers
Creators Name:Claes, G.R.F. and van Tienen, F.H.J. and Lindsey, P. and Krapels, I.P.C. and Helderman-van den Enden, A.T.J.M. and Hoos, M.B. and Barrois, Y.E.G. and Janssen, J.W.H. and Paulussen, A.D.C. and Sels, J.W.E.M. and Kuijpers, S.H.H. and van Tintelen, J.P. and van den Berg, M.P. and Heesen, W.F. and Garcia-Pavia, P. and Perrot, A. and Christiaans, I. and Salemink, S. and Marcelis, C.L.M. and Smeets, H.J.M. and Brunner, H.G. and Volders, P.G.A. and van den Wijngaard, A.
Abstract: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.
Keywords:Hypertrophy, Hypertrophic Cardiomyopathy, Hypertension, Risk Factors, Genetics, Mutation
Source:European Heart Journal
Publisher:Oxford University Press
Page Range:1815-1822
Date:14 June 2016
Official Publication:https://doi.org/10.1093/eurheartj/ehv522
PubMed:View item in PubMed

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