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The embryological basis of subclinical hypertrophic cardiomyopathy

Lookup NU author(s): Dr Janet Kerwin, Emerita Professor Susan Lindsay



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation.

Publication metadata

Author(s): Captur G, Ho CY, Schlossarek S, Kerwin J, Mirabel M, Wilson R, Rosmini S, Obianyo C, Reant P, Bassett P, Cook AC, Lindsay S, McKenna WJ, Mills K, Elliott PM, Mohun TJ, Carrier L, Moon JC

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2016

Volume: 6

Online publication date: 21/06/2016

Acceptance date: 24/05/2016

Date deposited: 18/08/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/srep27714


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Funder referenceFunder name
NIHR University College London Hospitals Biomedical Research Centre at Barts Hospital
DZHK (German Center for Cardiovascular Research)
European Society of Cardiology (ESC, EACVI)
German Ministry of Research and Education (BMBF)
University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital
11Leducq Foundation
11Leducq Foundation
532772National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC)
2415777th Framework Program of the European Union ("BIG-HEART")
CVD04Leducq Foundation
U117562103Medical Research Council
WT100160Wellcome Trust