The C11ORF74 interacts with the IFT-A complex via the IFT122 subunit and is accumulated at the distal tip in the absence of an IFT-A subunit IFT139 suggesting that at least a fraction of C11ORF74 molecules can be transported towards the ciliary tip by associating with the IFT-A complex although its majority might be out of cilia at steady state.
IFT122 mutations associated with cranioectodermal dysplasia 1 cause defects in ciliary protein trafficking but not ciliogenesis when expressed in cells lacking endogenous IFT122 (IFT122 KO).
All the nine probands with syndromic craniosynostosis were found to carry the possibly causative variants among which three variants including two missense mutations in IFT122 gene in SMC1A gene and a frameshift mutation in TWIST1 gene have never been reported in patients before.
Using a panel of skeletal dysplasias genes including 11 related to SRP we identified biallelic mutations in IFT122 in a fetus with a typical phenotype of SRP-IV finally confirmed that this phenotype is a ciliopathy and adding to the list of ciliopathies with major skeletal involvement.
The three patients had different novel compound heterozygous mutations in IFT122. Consequently we compared these three patients to those previously described with IFT122 mutations. Thus our report serves to add 6 novel mutations to the IFT122 mutation spectrum and to contribute to the IFT122-related clinical characterization.
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