Novel ELN mutation in a Japanese family with a severe form of supravalvular aortic stenosis

Mol Genet Genomic Med. 2019 Nov;7(11):e986. doi: 10.1002/mgg3.986. Epub 2019 Sep 27.


Background: Supravalvular aortic stenosis (SVAS) is one of the congenital cardiovascular diseases characterized by stenosis of the aorta. The stenotic lesions occur anywhere above the aortic valve in the aortic tree as well as pulmonary arteries and eventually leads to circulatory failure. 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.

Methods: Fluorescent In situ hybridization (FISH) analysis and gene sequencing were performed in a two-generation family in which severe form of SVAS was diagnosed.

Results: None of the patients tested showed microdeletion of ELN, LIMK1, and D7S613. A novel nonsense mutation of ELN (c.160G>T (p.(Gly54*)), RNA not analyzed) was found in exon 3 in three members; two of them died suddenly due to rapid progression of SVAS with possible arrhythmia in early infancy. A point mutation in the 5' untranslated region, which was previously suggested to be associated with SVAS, did not co-segregate with the SVAS phenotype and found to be SNPs.

Conclusion: Our report shows a broad spectrum of clinical features in family members sharing the identical mutations, suggesting a potential contribution of modifier gene(s) or interactions with environmental factors.

Keywords: ELN; modifier gene; pulmonary artery stenosis; sudden death; supravalvular aortic stenosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aortic Stenosis, Supravalvular / diagnostic imaging
  • Aortic Stenosis, Supravalvular / genetics*
  • Asian People
  • Elastin / genetics*
  • Family Health
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant, Newborn
  • Japan
  • Male
  • Pedigree
  • Point Mutation*


  • ELN protein, human
  • Elastin