Novel mutations in the human elastin gene (ELN) causing isolated supravalvular aortic stenosis

Abstract

Abstract. Supravalvular aortic stenosis (SVAS), an inherited vascular disease, is caused by mutations in the elastin gene (ELN). Our aim was to identify novel mutations of ELN and to determine the expression of ELN in patients with SVAS. For screening mutations in ELN, we performed PCR-directed sequence analysis with genomic DNA isolated from SVAS patients and control subjects. Expression of ELN at the mRNA and protein levels were assessed by real-time PCR and Western blot analyses, respectively, using primary skin fibroblast cultures established from SVAS patients and control subjects. We identified two novel mutations of ELN, G297_A308del and Q700X, in two unrelated Korean patients with isolated SVAS. G297_A308del occurred de novo while Q700X was derived maternally. In the patient with G297_A308, elastin expression was not significantly altered at the mRNA level, but was reduced to ~50% of the normal control at the protein level. The elastin expression levels in the patient with Q700X were reduced to <50% of the normal controls at both the mRNA and protein levels. Our findings confirm that functional haploinsufficiency of elastin is responsible for the pathogenesis associated with isolated SVAS across different ethnic backgrounds.

Williams Syndrome Predisposes to Vascular Stiffness Modified by Antihypertensive Use and Copy Number Changes in NCF1

“…When the elastin gene is mutated or deleted, the resulting elastin insufficiency leads to multiple cardiovascular abnormalities. Most consistently described in these populations are focal arterial stenoses and hypertension 5, 6, 26, 27 . However, the severity of the vascular features in WS is variable.…”

A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia

“…Elastin is also a key component of transversalis fascia that complements the role of collagen by providing elasticity, which allows for the tissue to stretch and return to its original form. Mutations in the human elastin gene, ELN , cause cutis laxa 40 , which has been associated with an increased risk of inguinal hernias 14 and supravalvular aortic stenosis 41 . In connective tissue, the integration of elastin to the microfibril scaffold is guided by fibulins 42 ; EFEMP1 is a member of the fibulin gene family, and the EFEMP1 protein binds tropoelastin, the building block of the elastin protein 43 .…”

Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India

“…There are several similar reports in which synuclein levels have been estimated in the blood of PD patients,33 although these were found to be unaltered in such patients. As lymphocytes of several genetic disorders are used to screen plausible markers for disease progression,34 we purified the lymphocytes from PD patients and controls in order to assess Parkin expression in blood. Our results showed alteration of Parkin expression in PD patients exhibiting PARK2 deletions when compared with controls (figure 2, table 3).…”