Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients.

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.
Competing Interests: Competing interests: SU reports personal fees from Nidek, Chuo Sangio, Santen and Alcon outside the submitted work. AM reports grants from Pfizer Japan, Abbott Japan, Otsuka Pharmaceutical, Eisai, Alcon Japan, Novartis Pharma KK, SEED and Santen Pharmaceutical, and personal fees from Lion Japan outside the submitted work. In addition, AM has a patent hydrogel contact lens for gene treatment licensed. HT reports personal fees from Rohto Pharmaceutical, Takeda Pharmaceutical, Mitsubishi Tanabe, AbbVie, Daiichi Sankyo, Chuo Sangio, Sanofi, Nihon Tenganyaku, Alcon Pharma, Bayer and Graybug Vision, grants and personal fees from Nidek, Otsuka, Pfizer, Santen, Alcon, Novartis, Senju, Kowa and Wakamoto, grants from HOYA and Allergan Japan, and personal fees and non-financial support from Carl Zeiss Meditec outside the submitted work. In addition, HT has a patent pending with Nidek.
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