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Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches

Bonnet, Crystela,b,c; El-Amraoui, Azizb,c,d

doi: 10.1097/WCO.0b013e32834ef8b2

Purpose of review Usher syndrome (USH) is the most prevalent cause of hereditary deafness–blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies.

Recent findings Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing.

Summary Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

aInstitut de la Vision

bInserm UMRS587

cUPMC-Paris 6

dUnité de Génétique et Physiologie de l’Audition, Institut Pasteur, Paris, France

Correspondence to Aziz El-Amraoui, Unité de Génétique et Physiologie de l’Audition, Département de Neuroscience, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.