The cellular function of the usher gene product myosin VIIa is specified by its ligands.

Abstract

Defects in myosin Vlla are responsible for Usher Syndrome 1B (Weil et al., 1995). Human Usher syndrome (USH), named after the British ophthalmologist Charles Usher (Usher, 1914), is the most common hereditary form of combined blind-and deafness (~ 50% of cases in the developed countries). USH designates a group of clinically and genetically heterogeneous disorders with hearing loss and retinitis pigmentosa (RP). Three different USH types (USH1, 2 and 3; see Table 1) can be distinguished according to the degree of clinical symptomes. USH1 is the most severe subtype, characterized by severe to profound congenital sensorineuronal deafness, constant vestibular dysfunction (balance deficiency) and prepubertal onset of retinitis pigmentosa. USH1 is genetically heterogeneous. Out of at least seven distinct genetic loci(USH1A-G)four corresponding genes have been identified, namelyUSH1 B,C,D, andF(Mustapha et al., 2002; Petit, 2001; Table 1).USH1Bencodes for the molecular motor protein myosin Vlla (Weil et al., 1995),USHICencodes harmonin (Bitner-Glindzicz et al., 2000; Verpy et al., 2000), a scaffold protein containing PDZ-domains, motifs which are known to organize supramolecular protein complexes (Sheng and Sala, 2001). Mutations in the cadherinrelated proteins, cadherin 23 (Cdh23) and protocadherin 15 (PCdh15) underline USH1D and USH1F, respectively (Bolz et al., 2001, 2002; Bork et al., 2001; Ahmed et al., 2001; Alagramam et al., 2001a b).