Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. Issue 10 (17th June 2019)

• Record Type: Journal Article
• Authors: Koyanagi, Yoshito; Akiyama, Masato; Nishiguchi, Koji M; Momozawa, Yukihide; Kamatani, Yoichiro; Takata, Sadaaki; Inai, Chihiro; Iwasaki, Yusuke; Kumano, Mikako; Murakami, Yusuke; Omodaka, Kazuko; Abe, Toshiaki; Komori, Shiori; Gao, Dan; Hirakata, Toshiaki; Kurata, Kentaro; Hosono, Katsuhiro; Ueno, Shinji; Hotta, Yoshihiro; Murakami, Akira; Terasaki, Hiroko; Wada, Yuko; Nakazawa, Toru; Ishibashi, Tatsuro; Ikeda, Yasuhiro; Kubo, Michiaki; Sonoda, Koh-Hei
• Is Part Of: Journal of medical genetics. Volume 56:Issue 10(2019)
• Page Start: 662
• Page End: 670
• Publication Date: 2019-06-17
• Subjects: retinitis pigmentosa -- genetic epidemiology -- next-generation sequencing; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2018-105691
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: The genetic profile of retinitis pigmentosa (RP) in East Asian populations has not been well characterised. Therefore, we conducted a large-scale sequencing study to investigate the genes and variants causing RP in a Japanese population. Methods: A total of 1209 Japanese patients diagnosed with typical RP were enrolled. We performed deep resequencing of 83 known causative genes of RP using next-generation sequencing. We defined pathogenic variants as those that were putatively deleterious or registered as pathogenic in the Human Gene Mutation Database or ClinVar database and had a minor allele frequency in any ethnic population of ≤0.5% for recessive genes or ≤0.01% for dominant genes as determined using population-based databases. Results: We successfully sequenced 1204 patients with RP and determined 200 pathogenic variants in 38 genes as the cause of RP in 356 patients (29.6%). Variants in six genes ( EYS, USH2A, RP1L1, RHO, RP1 and RPGR ) caused RP in 65.4% (233/356) of those patients. Among autosomal recessive genes, two known founder variants in EYS [p.(Ser1653fs) and p.(Tyr2935*)] and four East Asian-specific variants [p.(Gly2752Arg) in USH2A, p.(Arg658*) in RP1L1, p.(Gly2186Glu) in EYS and p.(Ile535Asn) in PDE6B ] and p.(Cys934Trp) in USH2A were found in ≥10 patients. Among autosomal dominant genes, four pathogenic variants [p.(Pro347Leu) in RHO, p.(Arg872fs) in RP1, p.(Arg41Trp) in CRX and p.(Gly381fs) in PRPF31 ] were found in ≥4 patients, while these variants were unreported or extremely rare in both East Asian and non-East Asian population-based databases. Conclusions: East Asian-specific variants in causative genes were the major causes of RP in the Japanese population.