CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome

The objective of this study was to determine whether genetic variants in known heart developmental pathways act synergistically in this setting to increase the risk for CHD, specifically BAV, in TS. We analyzed 208 whole exomes from girls and women with TS and performed gene-based variant enrichment analysis and rare-variant association testing to identify variants associated with BAV in TS. Notably, rare variants inCRELD1 were significantly enriched in individuals with TS who had BAV compared to those with structurally normal hearts. CRELD1 is a protein that functions as a regulator of calcineurin/NFAT signaling, and rare variants inCRELD1 have been associated with both syndromic and non-syndromic CHD. This observation supports the hypothesis that genetic modifiers outside the X chromosome that lie in known heart development pathways may influence CHD risk in TS.
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research