Letter by Yilmaz Et Al Regarding Article, Analysis of Dystrophin Deletion Mutations Predicts Age of Cardiomyopathy Onset In Becker Muscular Dystrophy

Letter by Yilmaz Et Al Regarding Article, Analysis of Dystrophin Deletion Mutations Predicts Age of Cardiomyopathy Onset In Becker Muscular Dystrophy
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  See discussions, stats, and author profiles for this publication at: Letter by Yilmaz et al Regarding Article,"Analysis of Dystrophin Deletion MutationsPredicts Age of Cardiomyopathy...  Article   in  Circulation Cardiovascular Genetics · April 2010 DOI: 10.1161/CIRCGENETICS.109.933614 · Source: PubMed CITATIONS 2 READS 11 3 authors , including: Some of the authors of this publication are also working on these related projects: Advanced cardiovascular health and imaging informatics   View projectAli YilmazUniversitätsklinikum Münster 72   PUBLICATIONS   1,446   CITATIONS   SEE PROFILE Steffen Erhard PetersenQueen Mary, University of London 241   PUBLICATIONS   5,592   CITATIONS   SEE PROFILE All content following this page was uploaded by Steffen Erhard Petersen on 21 January 2017. The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the srcinal documentand are linked to publications on ResearchGate, letting you access and read them immediately.    1942-3268American Heart Association. All rights reserved. Print ISSN: 1942-325X. Online ISSN:2010 Copyright ©Avenue, Dallas, TX 72514Circulation: Cardiovascular Genetics is published by the American Heart Association. 7272 Greenville DOI: 10.1161/CIRCGENETICS.109.933614 2010;3;e1; Circ Cardiovasc Genet  Ali Yilmaz, Joseph Suttie and Steffen E. Petersen Predicts Age of Cardiomyopathy Onset in Becker Muscular Dystrophy''Letter by Yilmaz et al Regarding Article, ''Analysis of Dystrophin Deletion Mutations the World Wide Web at: The online version of this article, along with updated information and services, is located Information about reprints can be found online at  journalpermissions@lww.com410-528-8550. E-mail:Health, 351 West Camden Street, Baltimore, MD 21201-2436. Phone: 410-528-4050. Fax: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters Kluwer Subscriptions: Information about subscribing to Circulation: Cardiovascular Genetics is online at  by guest on May 18, 2011circgenetics.ahajournals.orgDownloaded from   Correspondence Letter by Yilmaz et al Regarding Article,“Analysis of Dystrophin Deletion MutationsPredicts Age of Cardiomyopathy Onset in BeckerMuscular Dystrophy” To the Editor: The study by Kaspar et al 1 merits and demands great attentionbecause it nicely demonstrates the importance of integrating proteinstructure information in genotype–phenotype correlation studies.The authors not only demonstrate that the locus of dystrophin genemutation is associated with the time of onset (early versus late) of cardiomyopathy but also show that genetic dystrophin mutations thatresult in the disruption of spectrin repeat phasing (in the rod domainof the dystrophin protein) lead to early onset of cardiomyopathy,despite the absence of any differences in myocardial dystrophinexpression compared with those with dystrophin mutations withoutspectrin repeat phasing disruption.Unfortunately, there is one essential limitation in this (partlyretrospective) study that severely weakens the authors’ conclusions.Assessment of cardiomyopathy was based only on (1) routineclinical echocardiographic results comprising calculation of leftventricular diameters, ejection fraction, and fractional shortening and(2) chest radiograph measuring the heart-to-lung ratio. However, asstated by the authors themselves, cardiomyopathy in patients withmuscular dystrophy is often not diagnosed until cardiac symptomsmanifest, in particular, when conventional diagnostic methods suchas 2D or M-mode echocardiography are used. In this context, recentstudies have convincingly demonstrated that initial or subclinicalcardiac dysfunction can be diagnosed early and adequately by usingtissue Doppler echocardiography or cardiovascular MRI (CMR)before reduction in systolic function does occur. For example,Mertens et al 2 have demonstrated that segmental reductions insystolic deformation parameters and in early diastolic myocardialvelocities can be detected in patients with Duchenne musculardystrophy with normal global systolic function, using tissue Dopplerechocardiography. Similar results were obtained by Ashford et al 3 when CMR tagging was used for myocardial strain analysis. More-over, recent CMR-based studies have revealed that (sometimes evenextensive) myocardial fibrosis can be detected by late gadoliniumenhancement CMR even in patients with muscular dystrophy withnormal cardiac diameters and systolic function and consequentlynormal results based on conventional echocardiography. 4,5 Therefore, we argue that conventional echocardiographic methods(as applied in this study) are not sufficient to evaluate cardiomyop-athy in patients with muscular dystrophy and suggest that intriguingapproach of these authors in evaluating the genotype–phenotypecorrelation with concomitant consideration of changes in dystrophinprotein structure in patients with muscular dystrophy should becarefully interpreted as long as verification of their results based oncomprehensive CMR data is not achieved. Disclosures None. Ali Yilmaz, MD  Division of Cardiology Robert-Bosch-KrankenhausStuttgart, Germany Joseph Suttie, MD  Department of Cardiovascular MedicineUniversity of Oxford Centre for Clinical Magnetic Resonance ResearchUniversity of Oxford Oxford, United Kingdom Steffen E. Petersen, MD, DPhil Centre Lead for Advanced Cardiovascular ImagingWilliam Harvey Research Institute Barts and The London NIHR Biomedical Research Unit The London Chest Hospital London, United Kingdom References 1. Kaspar R, Allen H, Ray W, Flanigan K, Mendell J, Monatanaro F.Analysis of dystrophin deletion mutations predicts age of cardiomyopathyonset in Becker muscular dystrophy.  Circ Cardiovasc Genet  . 2009;2:544–551.2. Mertens L, Ganame J, Claus P, Goemans N, Thijs D, Eyskens B, Van LD,Bijnens B, D’hooge J, Sutherland GR, Buyse G. Early regional myo-cardial dysfunction in young patients with Duchenne muscular dystrophy.  J Am Soc Echocardiogr  . 2008;21:1049–1054.3. Ashford MW Jr, Liu W, Lin SJ, Abraszewski P, Caruthers SD, ConnollyAM, Yu X, Wickline SA. Occult cardiac contractile dysfunction indystrophin-deficient children revealed by cardiac magnetic resonancestrain imaging.  Circulation . 2005;112:2462–2467.4. Puchalski MD, Williams RV, Askovich B, Sower CT, Hor KH, Su JT,Pack N, Dibella E, Gottliebson WM. Late gadolinium enhancement:precursor to cardiomyopathy in Duchenne muscular dystrophy?  Int J Car-diovasc Imaging . 2009;25:57–63.5. Yilmaz A, Gdynia HJ, Baccouche H, Mahrholdt H, Meinhardt G, BassoC, Thiene G, Sperfeld AD, Ludolph AC, Sechtem U. Cardiacinvolvement in patients with Becker muscular dystrophy: new diagnosticand pathophysiological insights by a CMR approach.  J Cardiovasc Magn Reson . 2008;10:50. (Circ Cardiovasc Genet. 2010;3:e1.) © 2010 American Heart Association, Inc. Circ Cardiovasc Genet  is available at DOI: 10.1161/CIRCGENETICS.109.933614 e1  by guest on May 18, 2011circgenetics.ahajournals.orgDownloaded from  View publication statsView publication stats
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