Figure 3.

Overview of the primary cilium-related gene products involved in CS pathophysiology. Genes are clustered according to their function and location in the ciliary structures. Gene products labels are coloured after the suture sites (CS type legend) that are prevalently involved in the associated phenotypes (see Section 3.1 and Section 3.2 for details). The functional ciliary gene clusters and the associated phenotypes indicate some level of genotype/phenotype correlations: (i). the genes encoding adaptor proteins needed for the intraflagellar complex A-mediated retrograde transport (IFT122, IFT43, IFT140, WDR35, WDR19) are found mutated in phenotypes with midline CS, prevalently affecting the sagittal suture; (ii). genes encoding main players of the hedgehog pathway (SMO, GLI3, IHH, EVC and RAB23) are associated with more heterogeneous suture involvement, ranging from single sagittal or unicoronal CS, to bicoronal and multi-suture craniosynostoses; (iii). the genes products involved in the regulation of centrosome cycle, ciliary trafficking and cilium assembly are mutated in syndromes that may feature either midline CS (ASPM, MCPH1, CEP57, TMEM216, FLNA), or uni/bicoronal CS (NEK1, CEP120) up to multisuture CS (CDC45).