Abstract 15501: Rare Genomic Copy Number Variants Implicate New Candidate Genes for Bicuspid Aortic Valve

• DOI: 10.1161/circ.146.suppl_1.15501
• Publication Date: 2023-06-15T17:28:42Z
• Authors: Steven G Carlisle; Hasan Albasha; Hector I Michelena; Anna Sabate-Rotes; Lisa Bianco; Julie DeBacker; Laura Muino Mosquera; Angela T Yetman; Malenka Bissell; Maria Grazia Andr...; Ilenia Foffa; Dawn Hui; Anthony D Caffarelli; Yuli Y Kim; Dongchuan Guo; Rodolfo Citro; Margot De Marco; Justin Tretter; ; ; Neil A Hanchard; John W Belmont; Kim L McBride; Simon C Body; Siddharth K Prakash
• Keywords: SNP array; Candidate gene; Proband

Introduction: Bicuspid Aortic Valve (BAV), the most common adult congenital heart defect, is a major cause of aortic insufficiency or stenosis requiring valve replacement and thoracic aneurysms predisposing to acute dissections. The spectrum BAV ranges from early onset complications sporadic late disease. We determined frequency gene content rare genomic copy number variants (CNVs) in isolated cases. Methods: performed genome-wide SNP microarray analysis familial cases with UTHealth Research Registry (EBAV, n=394) elderly probands International Consortium (BAVCON, n=4216). CNVs were detected Illumina genotypes using PennCNV, QuantiSNP cnvPartition algorithms. compared 16,576 controls without known cardiovascular disease Database Genotypes Phenotypes. Only CNV calls >6 consecutive variants, >20 kb length, identified by at least two algorithms intersected genes included. For comparison, we assessed cohort left ventricular outflow tract obstructive lesions including (LVOTO, n=1561) identical methods. burden associations tested PLINK. Results: 84 large recurrent that are absent (<0.1%) controls. 34 overlap between LVOTO involve candidate interact each other during development. largest prevalent 8p23 duplications involving GATA4 (OR 340, CI: 42-2700). when mutated significantly enriched (n=135, P =1x10 -27 ). overall genic CNVs, specifically deletions, was also increased (empiric < 1x10 -5 ) higher younger EBAV than older BAVCON Conclusion: likely pathogenic more 10% cases, implicating alterations these loci pathogenesis BAV.