CEP290

CEP290, also known as centrosomal protein 290 kDa, is a gene in humans that encodes a protein with a molecular weight of approximately 290 kDa. This protein plays a crucial role in several cellular processes, most notably in the formation and function of cilia, which are hair-like structures that project from the surface of many cell types.

Function:

The CEP290 protein is primarily localized to the centrosomes, which are the main microtubule organizing centers (MTOCs) in animal cells. From the centrosomes, cilia extend. CEP290 is essential for the proper assembly and stability of the ciliary transition zone, a specialized region at the base of the cilium that acts as a gatekeeper, controlling the entry and exit of proteins into the cilium. It is also involved in the regulation of microtubule dynamics. The protein interacts with a number of other proteins involved in ciliogenesis and microtubule organization.

Clinical Significance:

Mutations in the CEP290 gene are associated with a wide range of genetic disorders, collectively known as ciliopathies. These disorders affect multiple organ systems and can present with a diverse array of symptoms. Some of the most common ciliopathies caused by CEP290 mutations include:

• Leber Congenital Amaurosis (LCA): A severe form of inherited retinal dystrophy that causes blindness from early infancy. CEP290 is the most frequently mutated gene in LCA.
• Joubert Syndrome (JBTS): A rare brain malformation characterized by a distinctive "molar tooth sign" on brain imaging, along with cerebellar ataxia, hypotonia, and intellectual disability.
• Senior-Loken Syndrome (SLSN): A disorder characterized by the combination of nephronophthisis (a kidney disease) and retinal degeneration.
• Meckel-Gruber Syndrome (MKS): A severe and often lethal disorder characterized by cystic kidneys, occipital encephalocele (a protrusion of the brain through an opening in the skull), and polydactyly (extra fingers or toes).
• Bardet-Biedl Syndrome (BBS): A genetically heterogeneous disorder characterized by retinal degeneration, obesity, polydactyly, learning difficulties, and kidney abnormalities.

The specific symptoms and severity of CEP290-related ciliopathies can vary depending on the particular mutation(s) present in the gene and the individual's genetic background. Diagnosis typically involves genetic testing to identify mutations in the CEP290 gene, along with clinical evaluation and imaging studies.

Gene Location:

The CEP290 gene is located on chromosome 12q21.33.