Heart valve diseases affect 3% of world population, and surgery is often the only therapeutic treatment. A genetic study performed on a family in which several members exhibited a Mitral Valve Prolapse (MVP) identified I328M mutation on one of the two PTPRF alternatively spliced isoforms.The longest isoform encodes the LAR receptor involved in neuronal development and axon guidance. LAR is a repressor of cell migration and proliferation, participates in adherens junctions and modulates small GTPases activity by interacting with the Rho/Rac regulator Trio. It also inhibits EGF/FGF signaling and interacts with Heparan Sulfates Proteoglycans (HSPGs) involved in cell-cell and cell-matrix adhesion. However, the identified mutation (I328M) only targets the short isoform (sPTPRF) whose structure, expression profile and functions remain unknown.
PTPRF thus appeared as a good MVP causing candidate gene as it may participate in signaling pathways involved in valve development and/or mechanical stress response.