11 September 2023
Disorders with a common genetic background
Published online 11 June 2010
Diseases such as Joubert syndrome and related disorders (JSRDs) and Meckel syndrome (MKS) are caused by genetic defects in the primary cilia — organelles present in most cell types — known as ciliopathies. JSRDs sometimes involve multiple organs and are characterized by symptoms such as ataxia (lack of movement coordination), hypotonia (abnormal loss of muscle tissue), oculomotor apraxia (difficulty in controlling eye movement) and irregular breathing patterns. MKS, by contrast, is a lethal condition that manifests prenatally or at birth and is mainly characterized by occipital encephalocele (abnormal protrusion of brain tissue through a skull defect), dysplastic kidneys and hepatic developmental defects.
An international team of scientists, including one from the Sultan Qaboos University Hospital in Oman, have managed to trace Joubert syndrome 2 (JBTS2) and MKS2 to mutations in the TMEM216 gene. The researchers speculate that the protein TMEM216, which gathers at the base of primary cilia, plays a role in ciliogenesis. Besides a decrease in the percentage of cells with cilia, mutations in the gene also caused a reduction in centrosome docking. The team showed that TMEM216 forms a complex with the Meckelin protein, which is encoded by another gene that is often mutated in JSRDs and MKS. This complex then mediates a pathway responsible for centrosome docking and the formation of cilia.
The findings of the paper are important because they highlight a role for a new family of tetraspan transmembrane proteins in disorders related to the primary cilia. They also support the theory of the presence of a genetic relationship between some of the different ciliopathies.
- Valente, EM. et al. Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nature Genetics. 30 May 2010. doi: 10.1038/ng.594