American journal of human genetics · 2024
Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Mansoorshahi Sara, Yetman Anji T, Bissell Malenka M, Kim Yuli Y, Michelena Hector I, De Backer Julie, Mosquera Laura Muiño, Hui Dawn S, Caffarelli Anthony, Andreassi Maria G, Foffa Ilenia, Guo Dongchuan, Citro Rodolfo, De Marco Margot, Tretter Justin T, Morris Shaine A, Body Simon C, Chong Jessica X, Bamshad Michael J, University of Washington Center for Rare Disease Research, BAVCon Investigators, EBAV Investigators, Milewicz Dianna M, Prakash Siddharth K
Аннотация
Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate genes that are associated with autosomal-dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants drive early-onset presentations of BAV disease.