Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.
Sara MansoorshahiAnji T YetmanMalenka M BissellYuli Y KimHector MichelenaDawn S HuiAnthony CaffarelliMaria G AndreassiIlenia FoffaDongchuan GuoRodolfo CitroMargot De MarcoJustin T TretterShaine A MorrisSimon C BodyJessica X ChongMichael J Bamshadnull nullnull nullnull nullDianna M MilewiczSiddharth K PrakashPublished in: medRxiv : the preprint server for health sciences (2024)
Bicuspid Aortic Valve (BAV) is the most common adult congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that early onset complications of BAV (EBAV) are driven by specific impactful genetic variants. We analyzed whole exome sequences (WES) to identify rare coding variants that contribute to BAV disease in 215 EBAV families. Predicted pathogenic variants of causal genes were present in 111 EBAV families (51% of total), including genes that cause BAV (8%) or heritable thoracic aortic disease (HTAD, 17%). After appropriate filtration, we also identified 93 variants in 26 novel 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 contribute to early onset complications of BAV disease.
Keyphrases
- early onset
- aortic valve
- genome wide
- aortic stenosis
- late onset
- copy number
- transcatheter aortic valve replacement
- transcatheter aortic valve implantation
- aortic valve replacement
- bioinformatics analysis
- genome wide identification
- risk factors
- dna methylation
- ejection fraction
- genome wide analysis
- coronary artery disease
- transcription factor
- gene expression
- heart failure
- pulmonary hypertension
- pulmonary arterial hypertension