![]() Traditionally, USH is subdivided into three clinical subclasses. In this review, we summarize the current developments in the field of USH. 7, 8, 9, 10, 11, 12, 13 These progresses on the molecular genetics have greatly advanced our understanding of the genetic causes and the pathogenesis of USH. This network may be critical for the development and maintenance of the sensorineural cells. Growing evidence suggests that these proteins are organized in a protein ‘interactome’ in both the inner ear and the retina. Although a common phenotype has been described in the different USH types, the identified USH genes encode for proteins from different protein classes and families. To date, only 1 USH3 locus has been described. Three genetic loci for USH2 (USH2A, USH2C and USH2D) have been reported and the corresponding genes have been determined. Five of these genes have been isolated (see ). Seven USH1 loci (USH1B–USH1H) have been identified so far by linkage analyses of USH1 families. Each USH subtype is genetically heterogeneous. Although this classification of USH remains in clinical use, atypical clinical types have been described that defy this easy classification. USH was historically divided into three clinical subtypes: USH type I, USH type II and USH type III (USH1, USH2 and USH3). 2, 3, 4, 5, 6 Progress on the molecular genetics and clinical research of USH has revealed broad genetic and clinical heterogeneity. 1, 2, 3 However, the syndrome is more common in regions with small, isolated, often inbred populations such as in Israel (Samarathians), Pakistan (Hutterites), France (Poitou-Charentes region), Northern Sweden, Finland and Accadian population of Louisiana, United States. 1, 2 Prevalence of USH in different populations ranging from 3.5 to 6.2 per 100 000, and a carrier rate of 1 in 100, have been reported. It has been estimated that USH accounts for between 3 and 6% of the congenitally deaf population, up to 8–33% of individuals with RP and 50% of the deaf–blind population. Vestibular dysfunction may also be a component. The blindness occurs from a progressive retinal degeneration termed retinitis pigmentosa (RP). Usher syndrome (USH) is a group of recessively inherited disorders characterized by deafness and vision loss. ![]() Understanding the molecular basis of phenotypic variation and pathogenesis of USH is important toward discovery of new molecular targets for diagnosis, prevention and treatment of this debilitating disorder. This review addresses genetics and pathological mechanisms of USH. ![]() A unifying hypothesis is that the USH proteins are integrated into a protein network that regulates hair bundle morphogenesis in the inner ear. Extensive information has emerged from mouse models and molecular studies regarding pathogenesis of this disorder and the wide phenotypic variation in both audiovestibular and/or visual function. The USH genes encode proteins of different classes and families, including motor proteins, scaffold proteins, cell adhesion molecules and transmembrane receptor proteins. Since the cloning of the first USH gene (MYO7A) in 1995, there have been remarkable advances in elucidating the genetic basis for this disorder, as evidence for 11 distinct loci have been obtained and genes for 9 of them have been identified. Three major clinical subtypes (USH type I, USH type II and USH type III) are distinguished on the basis of the severity of the hearing loss, the presence or absence of vestibular dysfunction and the age of onset of retinitis pigmentosa (RP). Usher syndrome (USH) comprises a group of autosomal recessively inherited disorders characterized by a dual sensory impairment of the audiovestibular and visual systems.
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