Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients

Author:

Koyanagi YoshitoORCID,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

Abstract

BackgroundThe 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.MethodsA 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.ResultsWe 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.ConclusionsEast Asian-specific variants in causative genes were the major causes of RP in the Japanese population.

Funder

Japan Agency for Medical Research and Development grants

Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science grant

Publisher

BMJ

Subject

Genetics (clinical),Genetics

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