Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2
| Autor: | M Stemerdink, B García-Bohórquez, E. van Wijk, Renske Schellens, Gema García-García, José M. Millán |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
VISUAL-FIELD LOSS
Usher syndrome CARRYING MUTATIONS Biology USH2A GENE Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Pathogenesis RETINITIS-PIGMENTOSA AUDIOGENIC-SEIZURES Retinitis pigmentosa SYNDROME TYPE IIA otorhinolaryngologic diseases Genetics medicine Inner ear Zebrafish Genetics (clinical) HEARING-LOSS ANKLE-LINK COMPLEX MOUSE MODEL medicine.disease biology.organism_classification Phenotype Human genetics PROTEIN-COUPLED RECEPTOR medicine.anatomical_structure Sensorineural hearing loss Neuroscience |
| Zdroj: | Human Genetics, 141, 737-758 Human Genetics Human Genetics, 141, 3-4, pp. 737-758 HUMAN GENETICS r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe instname |
| ISSN: | 0340-6717 |
| Popis: | Contains fulltext : 251721.pdf (Publisher’s version ) (Closed access) Usher syndrome (USH) is a rare, autosomal recessively inherited disorder resulting in a combination of sensorineural hearing loss and a progressive loss of vision resulting from retinitis pigmentosa (RP), occasionally accompanied by an altered vestibular function. More and more evidence is building up indicating that also sleep deprivation, olfactory dysfunction, deficits in tactile perception and reduced sperm motility are part of the disease etiology. USH can be clinically classified into three different types, of which Usher syndrome type 2 (USH2) is the most prevalent. In this review, we, therefore, assess the genetic and clinical aspects, available models and therapeutic developments for USH2. Mutations in USH2A, ADGRV1 and WHRN have been described to be responsible for USH2, with USH2A being the most frequently mutated USH-associated gene, explaining 50% of all cases. The proteins encoded by the USH2 genes together function in a dynamic protein complex that, among others, is found at the photoreceptor periciliary membrane and at the base of the hair bundles of inner ear hair cells. To unravel the pathogenic mechanisms underlying USH2, patient-derived cellular models and animal models including mouse, zebrafish and drosophila, have been generated that all in part mimic the USH phenotype. Multiple cellular and genetic therapeutic approaches are currently under development for USH2, mainly focused on preserving or partially restoring the visual function of which one is already in the clinical phase. These developments are opening a new gate towards a possible treatment for USH2 patients. |
| Databáze: | OpenAIRE |
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