Subsequently, the USH2A missense variant p.C759F was firstly reported to be associated with ARRP without hearing impairment in 2000, which was presumed to affect the disulfide bridge in the fifth laminin epidermal growth factor-like domain of the USH2A protein (Rivolta et al., 2000; Lenassi et al., 2015). This evidence concerns the gene USH2A and hearing loss disorder.