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

• Main Authors: Akira Inaba, Akiko Maeda, Akiko Yoshida, Kanako Kawai, Yasuhiko Hirami, Yasuo Kurimoto, Shinji Kosugi, Masayo Takahashi
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: International Journal of Molecular Sciences
• Subjects: retinitis pigmentosa; Usher syndrome; <i>USH2A</i>; inherited retinal degeneration; clinical sequence
• Online Access: https://www.mdpi.com/1422-0067/21/21/7817

<i>USH2A</i> is a common causal gene of retinitis pigmentosa (RP), a progressive blinding disease due to retinal degeneration. Genetic alterations in <i>USH2A</i> 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<i> USH2A</i>-associated RP (<i>USH2A</i>-RP) has been reported. Genetic and clinical characterization of <i>USH2A</i>-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 <i>USH2A </i>were identified in 36 of 525 (6.9%) patients and genetic features of <i>USH2A</i>-RP were characterized. Among 36 patients with <i>USH2A</i>-RP, 11 patients had syndromic RP with congenital hearing problems. Amino acid changes due to <i>USH2A</i> alterations were similarly located throughout entire regions of the <i>USH2A</i> 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 <i>USH2A</i>-RP.