We previously identified KIF7, a key ciliary component of the Sonic hedgehog (SHH) pathway, as being a causative gene for this syndrome, thus including ACLS in the group of ciliopathies.
The finding of known loss of function variants in ciliopathy associated genes, AHI1, BBS2 and BBS4 in addition to KIF7 mutations provides evidence for oligogenic inheritance in ACLS and suggests that this might contribute to the phenotypic variability of KIF7-related disorders.
Our data show the role of KIF7 in human primary cilia, especially in the Hedgehog pathway through the regulation of GLI targets, and expand the clinical spectrum of ciliopathies.