Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome
Barbara R. Pober, Mark Johnson, Zsolt Urban
Barbara R. Pober, Mark Johnson, Zsolt Urban
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Science in Medicine

Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome

Abstract

Williams-Beuren syndrome (WBS) is a microdeletion disorder caused by heterozygous loss of approximately 1.5-Mb pairs of DNA from chromosome 7. Patients with WBS have a characteristic constellation of medical and cognitive findings, with a hallmark feature of generalized arteriopathy presenting as stenoses of elastic arteries and hypertension. Human and mouse studies establish that defects in the elastin gene, leading to elastin haploinsufficiency, underlie the arteriopathy. In this review we describe potential links between elastin expression and arteriopathy, possible explanations for disease variability, and current treatment options and their limitations, and we propose several new directions for the development of nonsurgical preventative therapies based on insights from elastin biology.

Authors

Barbara R. Pober, Mark Johnson, Zsolt Urban

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Figure 2

The WBS critical region.

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The WBS critical region. The chromosome 7q11.23 microdeletion, with the ...
The chromosome 7q11.23 microdeletion, with the loss of 26–28 genes, that is responsible for WBS. Selected genes are labeled. Duplicons predispose to NAHR. More than 90% of WBS patients have the ~1.55-Mb pair deletion extending from FKBP6 to GTF2I, while approximately 5% have the slightly larger deletion of 1.84-Mb pairs. Very rare patients have atypical deletions smaller than the common deletion. Schematics of atypical deletions are shown on right and include a very small deletion encompassing ELN and an adjacent gene; a typical centromeric breakpoint but not the common telomeric breakpoint; and a typical telomeric breakpoint but not the typical centromeric breakpoint. Not all genes are shown; see ref. 20 for a complete list of genes. WBSCR, WBS critical region.