Mutation of FOP/FGFR1OP in mice recapitulates human short rib-polydactyly ciliopathy.

Olivier Cabaud, Régine Roubin, Audrey Comte, Virginie Bascunana, Arnauld Sergé, Fatima Sedjaï, Daniel Birnbaum, Olivier Rosnet, Claire Acquaviva

Human molecular genetics 2018 Oct 01

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Skeletal dysplasias are a clinically and genetically heterogeneous group of bone and cartilage disorders. A total of 436 skeletal dysplasias are listed in the 2015 revised version of the nosology and classification of genetic skeletal disorders, of which nearly 20% are still genetically and molecularly uncharacterized. We report the clinical and molecular characterization of a lethal skeletal dysplasia of the short-rib group caused by mutation of the mouse Fop gene. Fop encodes a centrosomal and centriolar satellite (CS) protein. We show that Fop mutation perturbs ciliogenesis in vivo and that this leads to the alteration of the Hedgehog signaling pathway. Fop mutation reduces CSs movements and affects pericentriolar material composition, which probably participates to the ciliogenesis defect. This study highlights the role of a centrosome and CSs protein producing phenotypes in mice that recapitulate a short rib-polydactyly syndrome when mutated.

Citation

Olivier Cabaud, Régine Roubin, Audrey Comte, Virginie Bascunana, Arnauld Sergé, Fatima Sedjaï, Daniel Birnbaum, Olivier Rosnet, Claire Acquaviva. Mutation of FOP/FGFR1OP in mice recapitulates human short rib-polydactyly ciliopathy. Human molecular genetics. 2018 Oct 01;27(19):3377-3391