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
N1 - Funding Information:
This work was supported by National Key Research and Developmental Program of China grants 2016YFC1000600, 2018YFC1004700, and 2018YFC1003900, Strategic Priority Research Program of the Chinese Academy of Sciences grant XDB19000000, National Natural Science Foundation of China grants 31890780, 31630050, 31771668, 31871514, 31601160, and 81571495, Major Program of Development Foundation of Hefei Centre for Physical Science and Technology grant 2018ZYFX005, and Fundamental Research Funds for the Central Universities grants YD2070003006, WK207000135, and WK207000136. The authors declare no competing financial interests.
Funding Information:
We are grateful to all the participants for their cooperation. We thank Li Wang at the Center of Cryo-Electron Microscopy, Zhejiang University, for her technical assistance on TEM and the Al-Khair Test Lab, Abbottabad, Pakistan, for providing facilities to perform semen analysis. We thank Dr. Qing Wei (Shanghai Institutes for Biological Sciences) for his valuable suggestions and Dr. Fang Wang, Dr. Manan Khan Jadoon, and other members of the Q. Shi laboratory for comments and advice. This work was supported by National Key Research and Developmental Program of China grants 2016YFC1000600, 2018YFC1004700, and 2018YFC1003900, Strategic Priority Research Program of the Chinese Academy of Sciences grant XDB19000000, National Natural Science Foundation of China grants 31890780, 31630050, 31771668, 31871514, 31601160, and 81571495, Major Program of Development Foundation of Hefei Centre for Physical Science and Technology grant 2018ZYFX005, and Fundamental Research Funds for the Central Universities grants YD2070003006, WK207000135, and WK207000136. The authors declare no competing financial interests. Author contributions: B. Zhang, T. Li, A. Ma, Y. Li, C. Yu, H. Yin, Q. Gao, X. Jiang, Q. Tao, Q. Hao, H. Fang, and H. Cheng performed the experiments; T. Khan, A. Ali, G. Murtaza, I. Khan, M. Zubair, H.M.J. Hussain, R. Khan, and A. Yousaf recruited the patients, performed semen analysis, and collected patient samples; J. Bao, F. Zhang, and C. Liu gave insightful discussion and constructive comments on the manuscript; L. Yuan and Y. Lu provided technique assistance for TEM analysis; X. Xu and Y. Wang provided assistance for experiments with human respiratory epithelial cells; H. Zhang, J. Gao, and J. Zhou performed the WES sequencing and WES data analysis. Q. Shi, H. Ma, and Y. Zhang conceived and supervised the study, designed and analyzed experiments, and wrote the manuscript.
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
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U2 - 10.1002/ajmg.a.35784
DO - 10.1002/ajmg.a.35784
M3 - Article
C2 - 23401415
AN - SCOPUS:84874196863
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 -