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DMD mutation and LTBP4 haplotype do not predict onset of left ventricular dysfunction in Duchenne muscular dystrophy

Published online by Cambridge University Press:  16 May 2018

Charlotte S. Van Dorn
Affiliation:
Department of Pediatric and Adolescent Medicine, Divisions of Pediatric Critical Care Medicine and Pediatric Cardiology, Mayo Clinic, Rochester, MN, USA
Michael D. Puchalski
Affiliation:
Department of Pediatrics, Division of Cardiology, University of Utah, Salt Lake City, UT, USA
Hsin-Yi Weng
Affiliation:
Department of Pediatrics, Division of Cardiology, University of Utah, Salt Lake City, UT, USA
Steven B. Bleyl
Affiliation:
Department of Pediatrics, Division of Medical Genetics, University of Utah, Salt Lake City, UT, USA
Russell J. Butterfield
Affiliation:
Department of Pediatrics, Division of Neurology, University of Utah, Salt Lake City, UT, USA
Richard V. Williams*
Affiliation:
Department of Pediatrics, Division of Cardiology, University of Utah, Salt Lake City, UT, USA
*
Author for correspondence: R. V. Williams, MD, Department of Pediatrics, Division of Pediatric Cardiology, University of Utah, 81 N. Mario Capecchi Drive, Salt Lake City, UT 84113, USA. Tel: 801 213 7641; Fax: 801 213 7778; E-mail: Richard.Williams@hsc.utah.edu

Abstract

Cardiomyopathy develops in >90% of Duchenne muscular dystrophy (DMD) patients by the second decade of life. We assessed the associations between DMD gene mutations, as well as Latent transforming growth factor-beta-binding protein 4 (LTBP4) haplotypes, and age at onset of myocardial dysfunction in DMD. DMD patients with baseline normal left ventricular systolic function and genotyping between 2004 and 2013 were included. Patients were grouped in multiple ways: specific DMD mutation domains, true loss-of-function mutations (group A) versus possible residual gene expression (group B), and LTBP4 haplotype. Age at onset of myocardial dysfunction was the first echocardiogram with an ejection fraction <55% and/or shortening fraction <28%. Of 101 DMD patients, 40 developed cardiomyopathy. There was no difference in age at onset of myocardial dysfunction among DMD genotype mutation domains (13.7±4.8 versus 14.3±1.0 versus 14.3±2.9 versus 13.8±2.5, p=0.97), groups A and B (14.4±2.8 versus 12.1±4.4, p=0.09), or LTBP4 haplotypes (14.5±3.2 versus 13.1±3.2 versus 11.0±2.8, p=0.18). DMD gene mutations involving the hinge 3 region, actin-binding domain, and exons 45–49, as well as the LTBP4 IAAM haplotype, were not associated with age of left ventricular dysfunction onset in DMD.

Type
Original Articles
Copyright
© Cambridge University Press 2018 

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DMD mutation and LTBP4 haplotype do not predict onset of left ventricular dysfunction in Duchenne muscular dystrophy
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DMD mutation and LTBP4 haplotype do not predict onset of left ventricular dysfunction in Duchenne muscular dystrophy
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