Ciliopathy: Usher syndrome

Usher syndrome (USH) is an autosomal recessive syndromic ciliopathy characterized by sensorineural hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. There are three clinical types depending on the severity and age of onset of the symptoms; in addition, ten genes are reported to be causative of USH, and six more related to the disease. These genes encode proteins of a diverse nature, which interact and form a dynamic protein network called the "Usher interactome". In the organ of Corti, the USH proteins are essential for the correct development and maintenance of the structure and cohesion of the stereocilia. In the retina, the USH protein network is principally located in the periciliary region of the photoreceptors, and plays an important role in the maintenance of the periciliary structure and the trafficking of molecules between the inner and the outer segments of photoreceptors. (PMID: 34201633) The cells affected by USH are the photoreceptors in the retina, and the hair cells of the cochlea and vestibular system, each of which presents ciliary-like structures, namely, the stereocilia and the connecting cilium, respectively. Regarding the inner ear, technically only the vestibular sensory cells present a genuine microtubule-based cilium at the vertex of the V-shaped hair bundle, which is the kinocilium; this bundle is only present during development in the cochlear hair cells, before subsequently disappearing. Nonetheless, this cilium is present during certain stages, and the stereocilia-microvilli resemble ciliary formations. Consequently, many specialists consider USH to be a ciliopathy, which is defined as a group of pathologies that arise from defects in genes that participate in the structure or signaling of cilia. Nonetheless, the use of the term ciliopathy to define USHis controversial. Even though some authors do not include USH in this category, others incorporate USH into the retinal ciliopathies group. Even though the USH proteins are not ciliary proteins, they are clearly essential for the function of photoreceptor cilia and USH should at least be considered a second-order ciliopathy. (PMID: 34201633)

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