Abstract
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 (9,455bp 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 527-533 |
| Number of pages | 7 |
| Journal | American Journal of Medical Genetics, Part A |
| Volume | 161 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2013 |
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Keywords
- Bicuspid valve aorta
- DNA polymorphisms
- Elastin
- Supravalvular aortic stenosis
- Williams-Beuren syndrome
ASJC Scopus subject areas
- Genetics(clinical)
- Genetics
Cite this
Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams-Beuren syndrome. / Delio, Maria; Pope, Kathleen; Wang, Tao; Samanich, Joy; Haldeman-Englert, Chad R.; Kaplan, Paige; Shaikh, Tamim H.; Cai, Jinlu; Marion, Robert W.; Morrow, Bernice E.; Babcock, Melanie.
In: American Journal of Medical Genetics, Part A, Vol. 161, No. 3, 03.2013, p. 527-533.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams-Beuren syndrome
AU - Delio, Maria
AU - Pope, Kathleen
AU - Wang, Tao
AU - Samanich, Joy
AU - Haldeman-Englert, Chad R.
AU - Kaplan, Paige
AU - Shaikh, Tamim H.
AU - Cai, Jinlu
AU - Marion, Robert W.
AU - Morrow, Bernice E.
AU - Babcock, Melanie
PY - 2013/3
Y1 - 2013/3
N2 - 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 (9,455bp 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.
AB - 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 (9,455bp 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.
KW - Bicuspid valve aorta
KW - DNA polymorphisms
KW - Elastin
KW - Supravalvular aortic stenosis
KW - Williams-Beuren syndrome
UR - http://www.scopus.com/inward/record.url?scp=84874196863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874196863&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.35784
DO - 10.1002/ajmg.a.35784
M3 - Article
VL - 161
SP - 527
EP - 533
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -