The embryological basis of subclinical hypertrophic cardiomyopathy

By G. Captur, Carolyn Y. Ho, S. Schlossarek, J. Kerwin, M. Mirabel, Robert Wilson, S. Rosmini, Chinwe Obianyo, P. Réant, P. Bassett and 8 more. 2016

39 citations recorded by the source corpus.

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.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology

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In Cardiology and Cardiovascular Medicine

Daniel Rueckert

Citations in the corpus

Learning Interpretable Anatomical Features Through Deep Generative Models: Application to Cardiac Remodeling (2018, background): “For instance, hypertrophic cardiomyopathy (HCM), a leading cause of sudden death in adults [2], is an inherited disease of the heart muscle which manifests clinically with unexplained left ventricular (LV) hypertrophy and can occur in many diﬀerent patterns that are not readily quantiﬁable [3].”