![]() In this review, we focus on the progress towards novel therapies for Usher syndrome and how these can be applied to Usher-related hearing loss.Ĭlinically, Usher syndrome is differentiated into three distinct types-Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2), and Usher syndrome type 3 (USH3). The advent of genome editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9, has brought the promise of gene therapies within reach. Supportive techniques such as hearing aids or cochlear implants are the only options for those subtypes that are amenable. While some of the genes resulting in Usher syndrome have been identified for some time there has been limited progress in therapeutic options for hearing loss in these patients. Usher syndrome is the most common cause of deaf-blindness and an important etiology underlying autosomal recessive deafness. Usher syndrome is characterized by hearing loss, visual impairment due to retinitis pigmentosa (RP), and in some cases, vestibular dysfunction. The remaining ~20% of genetic hearing loss cases are syndromic.Īn example of syndromic hearing loss is Usher syndrome. To date, there have been more than 150 genes and 6000 causative variants implicated in genetic causes of hearing loss. Among the non-syndromic forms of HL, 60–75% of these are inherited in an autosomal recessive manner, 20–30% are autosomal dominant, with a small minority (~2%) resulting from X-linked or mitochondrial inheritance. Non-syndromic HL makes up eighty percent of cases of genetic hearing loss. Hearing loss is classified as syndromic if there are other clinical manifestations in addition to the hearing loss, and non-syndromic if hearing loss is the only symptom of the genetic variant. HL is often the result of a defect in a single gene which can be inherited in an autosomal dominant, autosomal recessive, X-linked, or mitochondrial manner. Approximately half of all cases of severe to profound hearing loss have a genetic basis. Estimates place the prevalence of disabling hearing loss at around 466 million people worldwide representing about 5% of the population. Hearing loss (HL) is the most common sensory deficit. Failure at any one of these steps will result in hearing reduction or loss. ![]() Through this process mechanical sound waves are converted into electrical impulses that travels down the vestibulocochlear nerve (CNVIII) to be processed by the brain. Movements of the stereocilia result in the opening of ion channels on the hair cells, producing an action potential. Vibrations propagate through the endolymph and deflect the stereocilia of hair cells in the organ of Corti. The cochlea is a spiral-shaped structure filled with potassium-rich endolymph. Here, sound waves are translated into mechanical vibrations and are passed down the bones of the middle ear, from the malleus to the incus to the stapes and through the oval window into the cochlea. The waves then travel down the canal and come in contact with the tympanic membrane, also known as the ear drum. ![]() ![]() Hearing begins when sound is funneled into the ear canal by the pinna. ![]() The ear can be divided into three anatomical sections-the outer ear (from the visible pinna to the ear canal), the middle ear (from the tympanic membrane to the oval window including the smallest bones in the body), and the inner ear (the semicircular canal, vestibule, and cochlea). As such, there is significant room for genetic changes leading to hearing loss. The ear is a highly evolved sensory organ with a complex mechanotransduction pathway. ![]()
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