Usher Syndrome: Genetics and Molecular Links of Hearing Loss and Directions for Therapy

Frontiers in Genetics
Meg WhatleyElaine Y M Wong

Abstract

Usher syndrome (USH) is an autosomal recessive (AR) disorder that permanently and severely affects the senses of hearing, vision, and balance. Three clinically distinct types of USH have been identified, decreasing in severity from Type 1 to 3, with symptoms of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP), and vestibular dysfunction. There are currently nine confirmed and two suspected USH-causative genes, and a further three candidate loci have been mapped. The proteins encoded by these genes form complexes that play critical roles in the development and maintenance of cellular structures within the inner ear and retina, which have minimal capacity for repair or regeneration. In the cochlea, stereocilia are located on the apical surface of inner ear hair cells (HC) and are responsible for transducing mechanical stimuli from sound pressure waves into chemical signals. These signals are then detected by the auditory nerve fibers, transmitted to the brain and interpreted as sound. Disease-causing mutations in USH genes can destabilize the tip links that bind the stereocilia to each other, and cause defects in protein trafficking and stereocilia bundle morphology, thereby inhibiting mechanosensory transduction. Thi...Continue Reading

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Citations

Mar 23, 2021·Frontiers in Cell and Developmental Biology·Laura Sánchez-BellverGemma Marfany

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Methods Mentioned

BETA
SANS
antisense oligonucleotide
transgenic
cochlear implants

Clinical Trials Mentioned

NCT03872479
NCT03780257
NCT02819856

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