In this study, we identified four novel pathogenetic mutations in Tibetan PFO patients, including GABRP rs201584759 (c.421C>T: p. R141C), GJB4 rs200602523 (c.292C>T: p. R98C), RTTN rs199568901 (c.5410G>A: E1804K), and USH2A rs144768593 (c.5608C>T: p. R1870W). This evidence concerns the gene RTTN and Patent foramen ovale.