Variations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish

The Genetics and Development of Heart Defects team in collaboration with the team of C. Jopling at the IGF (Inserm U1191) and the team of R. Rezsohazy (UCL, Belgium) has published a novel study in Nature Communications.

Bicuspid aortic valve (BAV) is the most common cardiac defect. Although highly heritable, few causal mutations have been identified. Here, the authors identify variants in the poly-histidine repeat motif of HOXA1. In vitro analysis shows that disruption of this motif leads to a significant reduction in protein half-life and defective transcriptional activity of HOXA1. In vivo assays indicates that these variants behave as dominant negatives leading abnormal valve development and that deletion of Hoxa1 results in BAV in mouse and zebrafish.