Truncating Variants Contribute to Hearing Loss and Severe Retinopathy in USH2A -Associated Retinitis Pigmentosa in Japanese Patients

is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in can lead to two types of RP, non-syndromic and syndromic RP, which is called Usher syndrome, with impairments of vision and hearing. The complexity of the genotype-phenotype correlation in -associated RP ( -RP) has been reported. Genetic and clinical characterization of -RP has not been performed in Japanese patients. In this study, genetic analyses were performed using targeted panel sequencing in 525 Japanese RP patients. Pathogenic variants of were identified in 36 of 525 (6.9%) patients and genetic features of -RP were characterized. Among 36 patients with -RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to alterations were similarly located throughout entire regions of the protein structure in non-syndromic and syndromic RP cases. Notably, truncating variants were detected in all syndromic patients with a more severe retinal phenotype as compared to non-syndromic RP cases. Taken together, truncating variants could contribute to more serious functional and tissue damages in Japanese patients, suggesting important roles for truncating mutations in the pathogenesis of syndromic -RP.