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**14** 

Jun Yang

*USA* 

**Usher Syndrome: Genes, Proteins, Models,** 

*Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah* 

Usher syndrome (USH) is an autosomal recessive genetic disease, characterized by both deafness and blindness. It was first described by Albrecht von Grafe, a German ophthalmologist, in 1858 (von Graefe, 1858) and then named after Charles Usher, a British ophthalmologist, who reported the inheritance of this disease on the basis of 69 cases in 1914 (Usher, 1914). USH is clinically heterogeneous and is categorized into three types, according to the severity of its hearing and vestibular symptoms (Smith et al., 1994; Petit, 2001). Type I (USH1) patients have congenital severe to profound deafness as well as vestibular dysfunction; Patients with USH2 exhibit congenital moderate degree of hearing loss and normal vestibular function; and those with USH3 display progressive hearing impairment and occasional vestibular dysfunction. The vision problem of all three types is manifested as retinitis pigmentosa (Hartong et al., 2006; Sadeghi et al., 2006; Fishman et al., 2007; Sandberg et al., 2008; Malm et al., 2011), showing early night and peripheral vision loss and eventual

USH is the most common genetic cause of combined blindness and deafness, occurring in about 1 in 23,000 people worldwide (Boughman et al., 1983; Keats and Corey, 1999; Hartong et al., 2006). It represents 50% of the blindness-deafness cases, 5% of all congenital deafness and 18% of retinitis pigmentosa (Millan et al., 2011). In Europe, USH1, USH2 and USH3 generally account for 25-44%, 56-75%, and 2% of all USH cases, respectively (Grondahl, 1987; Hope et al., 1997; Rosenberg et al., 1997; Spandau and Rohrschneider, 2002). Due to the regional founder effect, USH3 is much more common in Birmingham and Finland (Pakarinen et al., 1995; Hope et al., 1997). To date, there is no cure for this disease. USH patients mainly rely on early diagnosis and early education to adapt themselves to their

USH is genetically diverse besides its clinical heterogeneity. Currently, eleven loci have been identified (Hereditary hearing loss homepage and Hmani-Aifa et al., 2009), and nine genes on these loci are known. Among these genes, five are involved in USH1, three in USH2 and one in USH3 (Reiners et al., 2006; Williams, 2008; Millan et al., 2011). Although the functions of some USH genes are relatively clear now in the inner ear (see section 6), extensive work is still necessary to elucidate the functions of USH genes in both the inner ear and the retina.

**1. Introduction** 

central vision loss.

dual sensory loss.

**2. USH genes** 

**Molecular Mechanisms, and Therapies** 

