Parents

Ciliopathies are clinically and genetically heterogeneous disorders caused by dysfunction of the primary cilium, a nearly ubiquitous subcellular organelle playing key roles in the functioning of many adult tissues and during embryonic development. Many organs can be affected in ciliopathies, namely the central nervous system, the retina, the kidneys, the liver and the skeleton, either isolate or in variable combinations. Neurodevelopmental ciliopathies such as Joubert syndrome are always characterized by a malformation of the central nervous system (the so-called ‘molar tooth sign’), while skeletal ciliopathies, such as Jeune asphyxiating thoracic dystrophy, are invariably characterized by skeletal defects, such as narrow thorax with short ribs, short limbs and digital defects. Yet, there can be large clinical overlap among distinct ciliopathies and some severe forms, that are usually lethal, may present a combination of features of many ciliopathies. Similarly, there is genetic overlap, and mutations in the very same gene may result in different ciliopathy presentations. This is the case of CEP120, whose mutations may cause a spectrum of ciliopathies, as described later. The reason underlying this variability is still poorly understood. CEP120 mutations are recessively inherited, this means that both copies of the gene need to carry pathogenic alterations in order to manifest the disease. Affected individuals usually inherit each mutated copy of the gene from each unaffected parent. The prevalence of CEP120-related ciliopathies is unknown but predicted to be extremely rare, as only ten patients have been reported to date.