What causes ciliopathy phenotypes related to the CEP120 gene?
The CEP120 gene encodes for a protein that is involved in the correct formation of the primary cilium. Changes affecting both copies of the CEP120 gene can cause a spectrum of distinct ciliopathies (disorders related to malfunctioning of the primary cilium) involving one or more organs. In particular, CEP120 has been associated to neurodevelopmental ciliopathies (such as JS), skeletal ciliopathies (such as JATD) and more severe lethal ciliopathy phenotypes with multiorgan involvement.
What is needed to confirm the diagnosis of ciliopathies related to the CEP120 gene?
This diagnosis is confirmed by performing genetic testing in an affected individual, which enables the detection of pathogenic changes in both copies of the CEP120 gene.
There are two possible ways to identify such CEP120 changes:
- Since the syndrome is not highly recognizable, the most effective strategy would be the simultaneous analysis of CEP120 as part of a group of several ciliopathy-related genes through next-generation-sequencing techniques (either targeted panel sequencing, clinical exome or whole exome sequencing).
- If mutations in the CEP120 gene have already been identified in other family members, or if there is a specific suspicion towards this gene (for instance if the affected child is the offspring of consanguineous parents and a previous exam has shown a large region of homozygosity encompassing CEP120), the gene can be directly sequenced using conventional Sanger technique.
Large exonic or multi-exonic rearrangements of CEP120 have not been reported to date.
The genetic testing can be arranged by a clinical geneticist and involves the collection of a sample of blood or saliva from the affected individual (and eventually the parents). Analyzing the DNA of the patient and comparing it with the parents’ DNA may facilitate the detection of two CEP120 disease-causing changes in the child, one inherited from each parent.