To date, nine different pathogenic variants in CEP120 have been reported either in homozygosity or compound heterozygosity in ten families. These include truncating variants, splice site variants and missense variants affecting highly conserved amino acid residues. The c.595G>C (p.Ala199Pro) variant is the only recurring mutation, identified in four families with JATD and in a fetus affected by tectal and cerebellar dysgraphia with occipital encephalocele and skeletal defects. Unless a specific mutation has already been identified in another family member, genetic testing is usually performed with next generation sequencing approaches, by analyzing a panel of ciliopathy-related genes. Exon deletions/duplications and structural genomic abnormalities involving the CEP120 gene have not been reported to date.
CEP120 encodes for a centrosomal protein containing a coiled-coil domain, which is essential for microtubule organization and centriolar assembly and elongation. In a mouse knock-out model, Cep120 was found to play a fundamental role in neuronal migration and maintenance of the neural progenitor pool during neocortical development. Its depletion led to aberrant centriolar duplication and failure of formation and organization of cilia and centrosomes. This was confirmed in a Cep120 knockdown zebrafish model, displaying a severe ciliopathy phenotype with abnormal body curvature, hydrocephalus, and abnormal renal, head and craniofacial development, which displayed disorganized and shorter cilia in the pronephric duct and neural tube. Studies in fibroblasts from one affected individual demonstrated a marked reduction of cilia and abnormal number of centrioles. Similarly, CEP120 silencing in RPE1 cells resulted in shortening of centrioles and defect in formation of centrioles and cilia, mainly due to the impaired recruitment of CEP120 interactors, such as C2CD3 and Talpid3, to the distal ends of centrioles.
Useful resources:
https://databases.lovd.nl/shared/genes/CEP120
https://www.omim.org/entry/613446?search=cep120&highlight=cep120