The disease gene has been identified on the elastin gene (ELN) and two types of SVAS have been categorized; a familial type and an isolated type with the de novo mutation.
Elastin (ELN) insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing.
Rare alteration of the elastin (ELN) gene produces disease by impacting protein dosage (supravalvar aortic stenosis, Williams Beuren syndrome and Williams Beuren region duplication syndrome) and protein function (autosomal dominant cutis laxa).
Clinical symptoms that are associated with hemizygosity of the essential extracellular matrix protein elastin include premature aging of the skin and supravalvular aortic stenosis.
Sporadic and familial elastin mutations can occur in large vessel stenosis such as supravalvular aortic stenosis and narrowing of the descending aorta.
Thus, integrin β3-mediated signaling in SMCs links elastin deficiency and pathological stenosis, and inhibiting this pathway is an attractive therapeutic strategy for SVAS.
Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams-Beuren syndrome (WBS).
Elastin haploinsufficiency causes the cardiovascular complications associated with Williams-Beuren syndrome and isolated supravalvular aortic stenosis.
In vitro analysis using minigenes and cycloheximide showed that some selected frameshift mutant alleles are substrates of nonsense-mediated mRNA decay (NMD), confirming that the functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS.
In vitro analysis using minigenes and cycloheximide showed that some selected frameshift mutant alleles are substrates of nonsense-mediated mRNA decay (NMD), confirming that the functional haploinsufficiency of the ELN gene is the main pathomechanism underlying SVAS.
WBS is thought to be caused by haploinsufficiency of certain dosage-sensitive genes within the deleted region, and the feature of supravalvular aortic stenosis (SVAS) has been attributed to reduced elastin caused by deletion of ELN.
Elastin haploinsufficiency is responsible for a significant portion of the Williams syndrome (WS) phenotype including hoarse voice, supravalvar aortic stenosis (SVAS), hernias, diverticuli of bowel and bladder, soft skin, and joint abnormalities.
Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features.
WBS is thought to be caused by haploinsufficiency of certain dosage-sensitive genes within the deleted region, and the feature of supravalvular aortic stenosis (SVAS) has been attributed to reduced elastin caused by deletion of ELN.
Even though elastin and fibrillin-1 are the major structural components of elastic fibers, mutations in elastin and fibrillin-1 lead to narrowing of large arteries in supravalvular aortic stenosis and dilation of the ascending aorta in Marfan syndrome, respectively.
The results of this study confirm that reestablishing normal elastin levels is a logical objective for treating diseases of elastin insufficiency such as supravalvular aortic stenosis.
We report the results obtained in a mutation screening of the elastin gene in 28 patients with supravalvular aortic stenosis and other vascular abnormalities.
Our findings confirm that functional haploinsufficiency of elastin is responsible for the pathogenesis associated with isolated SVAS across different ethnic backgrounds.