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

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 approximately 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.