OP-071 Mutations in ARHGAP24 Encoding Filgap as a Cause of Mitral Valve Prolapse




Objective


Mitral valve prolapse (MVP) affects 2-4% of the general population and remains one of the most frequent indications for valvular surgery. Previous familial and pathophysiological studies suggest a complex pattern of inheritance. So far, FLNA is the only gene described in MVP. Recently, we showed that FLNA mutations deregulate the RhoA-Rac1 GTPases balance and provided evidences for a role of the Rac1 specific activating protein, FilGAP. Giving the tight interactions between FlnA and FilGAP, we hypothesized that FilGAP, encoded by ARHGAP24, could be involved in familial forms of MVP.




Methods


ARHGAP24 has been sequenced in a cohort of 95 MVP patients using a Next Generation Sequencing Target Enrichment assay. FilGAP functions were investigated in Hek293 cells. GAP activity, FlnA and PIP3 interactions were analyzed in pull-down, co-immunoprecipitations and dot blot using PIP-strips, respectively. Functional impacts of the mutations on cells adhesion were analyzed using XCelligence system, and their role in atrio-ventricular valve function studied by antisense morpholino based knocked-down of the ortholog of ARHGAP24 in zebrafish.

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Nov 30, 2016 | Posted by in CARDIOLOGY | Comments Off on OP-071 Mutations in ARHGAP24 Encoding Filgap as a Cause of Mitral Valve Prolapse

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