How to Cite this Article: Delio M, Pope K, Wang T, Samanich J, Haldeman-Englert CR, Kaplan P, Shaikh TH, Cai J, Marion RW, Morrow BE, Babcock M. 2013. Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams–Beuren syndrome. Am J Med Genet Part A 161A: 527–533.
Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams–Beuren syndrome†
Article first published online: 7 FEB 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 3, pages 527–533, March 2013
How to Cite
Delio, M., Pope, K., Wang, T., Samanich, J., Haldeman-Englert, C. R., Kaplan, P., Shaikh, T. H., Cai, J., Marion, R. W., Morrow, B. E. and Babcock, M. (2013), Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams–Beuren syndrome. Am. J. Med. Genet., 161: 527–533. doi: 10.1002/ajmg.a.35784
- Issue published online: 21 FEB 2013
- Article first published online: 7 FEB 2013
- Manuscript Accepted: 24 OCT 2012
- Manuscript Received: 22 JAN 2012
- Williams–Beuren syndrome;
- DNA polymorphisms;
- supravalvular aortic stenosis;
- bicuspid valve aorta
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). These defects occur with variable penetrance and expressivity, but the basis of this is unknown. To determine whether DNA variations in ELN could serve as genetic modifiers, we sequenced the 33 exons and immediately surrounding sequence of the ELN gene (9,455 bp of sequence) in 49 DNAs from patients with WBS and compared cardiovascular phenotypes. Four missense, and four novel intronic variants were identified from a total of 24 mostly intronic single nucleotide variations and one indel. Two missense changes were present in one patient each, one published, p.Gly610Ser in exon 27 (MAF, 0.003) and one novel, p.Cys714Tyr, in exon 33 (MAF, 0.001), were rare in the general population. To identify a statistical association between the variants identified here and cardiovascular phenotypes a larger cohort would be needed. © 2013 Wiley Periodicals, Inc.