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

Area of Science:

• Genetics
• Cardiovascular Medicine
• Molecular Biology

Background:

• Supravalvular aortic stenosis (SVAS) is an inherited vascular disease.
• Mutations in the elastin gene (ELN) are the known cause of SVAS.

Purpose of the Study:

• Identify novel mutations in the ELN gene in patients with SVAS.
• Determine the expression levels of ELN in SVAS patients.

Main Methods:

• PCR-directed sequence analysis of genomic DNA from SVAS patients and controls.
• Real-time PCR and Western blot analysis of ELN mRNA and protein levels in fibroblast cultures.

Main Results:

• Two novel ELN mutations (G297_A308del and Q700X) were identified in two unrelated Korean SVAS patients.
• Elastin protein levels were reduced by approximately 50% in one patient and <50% in another.
• Elastin mRNA levels were unaffected in one patient but reduced in the other.

Conclusions:

• Functional haploinsufficiency of elastin causes isolated SVAS.
• These findings are applicable across different ethnic backgrounds.