Novel mutation in EFCAB7 alters expression and interaction of Ellis-van Creveld ciliary proteins.

Ellis-van Creveld (EVC) syndrome (chondroectodermal dysplasia) is an autosomal recessive ciliopathy caused by mutations in one of the three genes, EVC, EVC2 and WDR35 (Valencia et al. 2009, Antony et al. 2017). Heterozygotes may present with a milder phenotype, Weyers syndrome (acrofacial dysostosis) (D'Asdia et al. 2013). The EVC and EVC2 proteins form a complex, whose localization at the base of cilia is regulated by two other ciliary proteins, EFCAB7 and IQCE. The ECH1 domain of EFCAB7 binds to the WEYER domain of EVC2. According to previous in vitro studies, EFCAB7 depletion causes the mislocalization of EVC-EVC2, and reduces the expression of IQCE but not of EVC and EVC2 (Pusapati et al. 2014).