Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients

Yoshito Koyanagi, Masato Akiyama, Koji M. Nishiguchi, Yukihide Momozawa, Yoichiro Kamatani, Sadaaki Takata, Chihiro Inai, Yusuke Iwasaki, Mikako Kumano, Yusuke Murakami, Kazuko Omodaka, Toshiaki Abe, Shiori Komori, Dan Gao, Toshiaki Hirakata, Kentaro Kurata, Katsuhiro Hosono, Shinji Ueno, Yoshihiro Hotta, Akira MurakamiHiroko Terasaki, Yuko Wada, Toru Nakazawa, Tatsuro Ishibashi, Yasuhiro Ikeda, Michiaki Kubo, Koh Hei Sonoda

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)662-670
Number of pages9
JournalJournal of medical genetics
Issue number10
Publication statusPublished - 2019 Oct 1


  • genetic epidemiology
  • next-generation sequencing
  • retinitis pigmentosa

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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