Bilateral semilunar valve disease in a child with partial deletion of the Williams-Beuren syndrome region is associated with elastin haploinsufficiency

Division of Cardiology, Cincinnati Children's Hospital, Cincinnati, Ohio 45229-3039, USA.
The Journal of heart valve disease (Impact Factor: 0.75). 06/2006; 15(3):352-5.
Source: PubMed


Elastin is an extracellular matrix protein that is the primary component of elastic fibers, and is expressed in the great vessels as well as the semilunar and atrioventricular valves. Elastin haploinsufficiency, resulting from mutation or deletion of the elastin gene, is an important clinical problem that is typically characterized by arteriopathy. Herein is described a patient with elastin haploinsufficiency due to partial deletion of the Williams-Beuren syndrome region, resulting in bilateral semilunar valve disease and arteriopathy. Histochemical analysis of the aortic valve revealed decreased and disorganized elastin with loss of the normal trilaminar cusp organization. These findings suggest that elastin has a role in the pathogenesis of semilunar valve disease.

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Available from: Colleen A Morris, Sep 04, 2014
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    • "Heart valves facilitate unidirectional blood flow during the cardiac cycle and this is largely achieved by highly organized layers of connective tissue that each offer distinct biomechanical properties to facilitate opening and closing of the valve leaflets or cusps [1], [2]. In healthy valves, connective tissue homeostasis is mediated by valve interstitial cells (VICs), which in turn are regulated by a monolayer of valve endothelial cells (VECs) that overly the valve surface. "
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    ABSTRACT: Heart valve disease affects up to 30% of the population and has been shown to have origins during embryonic development. Valvulogenesis begins with formation of endocardial cushions in the atrioventricular canal and outflow tract regions. Subsequently, endocardial cushions remodel, elongate and progressively form mature valve structures composed of a highly organized connective tissue that provides the necessary biomechanical function throughout life. While endocardial cushion formation has been well studied, the processes required for valve remodeling are less well understood. The transcription factor Scleraxis (Scx) is detected in mouse valves from E15.5 during initial stages of remodeling, and expression remains high until birth when formation of the highly organized mature structure is complete. Heart valves from Scx-/- mice are abnormally thick and develop fibrotic phenotypes similar to human disease by juvenile stages. These phenotypes begin around E15.5 and are associated with defects in connective tissue organization and valve interstitial cell differentiation. In order to understand the etiology of this phenotype, we analyzed the transcriptome of remodeling valves isolated from E15.5 Scx-/- embryos using RNA-seq. From this, we have identified a profile of protein and non-protein mRNAs that are dependent on Scx function and using bioinformatics we can predict the molecular functions and biological processes affected by these genes. These include processes and functions associated with gene regulation (methyltransferase activity, DNA binding, Notch signaling), vitamin A metabolism (retinoic acid biosynthesis) and cellular development (cell morphology, cell assembly and organization). In addition, several mRNAs are affected by alternative splicing events in the absence of Scx, suggesting additional roles in post-transcriptional modification. In summary, our findings have identified transcriptome profiles from abnormal heart valves isolated from E15.5 Scx-/- embryos that could be used in the future to understand mechanisms of heart valve disease in the human population.
    PLoS ONE 07/2014; 9(7):e101425. DOI:10.1371/journal.pone.0101425 · 3.23 Impact Factor
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    • "he interstitial cells . Disruptions in the developmental pro - cesses that lead to normal valve histomorphology and the dysfunction of the two major valve cell types have been shown to be responsible for a series of valve pathological conditions ( Rabkin et al . 2002 ; Leask et al . 2003 ; Armstrong & Bischoff 2004 ; Rabkin - Aikawa et al . 2004 ; Hinton et al . 2006 ) . As melanocyte precursors reach the heart during the early stages of valve development and per - sist into adulthood ( Brito & Kos 2008 ) , it is reasonable to expect that their dysfunction might lead to valve abnorm - alities . Deficits associated with the proper specification , differentiation and migration of neural crest cells an"
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