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Regional differences in genes and variants causing retinitis pigmentosa in Japan



To investigate the regional differences in the genes and variants causing retinitis pigmentosa (RP) in Japan

Study design

Retrospective multicenter study


In total, 1204 probands of each pedigree clinically diagnosed with nonsyndromic RP were enrolled from 5 Japanese facilities. The regions were divided into the Tohoku region, the Kanto and Chubu regions, and the Kyushu region according to the location of the hospitals where the participants were enrolled. We compared the proportions of the causative genes and the distributions of the pathogenic variants among these 3 regions.


The proportions of genetically solved cases were 29.4% in the Tohoku region (n = 500), 29.6% in the Kanto and Chubu regions (n = 196), and 29.7% in the Kyushu region (n = 508), which did not differ statistically (P = .99). No significant regional differences in the proportions of each causative gene in genetically solved patients were observed after correction by multiple testing. Among the 29 pathogenic variants detected in all 3 regions, only p.(Pro347Leu) in RHO was an autosomal dominant variant; the remaining 28 variants were found in autosomal recessive genes. Conversely, 78.6% (275/350) of the pathogenic variants were detected only in a single region, and 6 pathogenic variants (p.[Asn3062fs] in EYS, p.[Ala315fs] in EYS, p.[Arg872fs] in RP1, p.[Ala126Val] in RDH12, p.[Arg41Trp] in CRX, and p.[Gly381fs] in PRPF31) were frequently found in ≥ 4 patients in the single region.


We observed region-specific pathogenic variants in the Japanese population. Further investigations of causative genes in multiple regions in Japan will contribute to the expansion of the catalog of genetic variants causing RP.

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We acknowledge the staff of the Laboratory for Statistical Analysis and Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences. We would like to show our appreciation to J. Funatsu, T. Tachibana, K. Fujiwara, and S. Nakatake for collecting the samples and clinical data at Kyushu University Hospital. The patients were recruited through the Japan Retinitis Pigmentosa Registry Project (


This work was supported by Japan Agency for Medical Research and Development grants 17ek0109213h0002 (to K.M.N.) and by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (grant 17K111447, to Y.H.).

These funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Correspondence to Masato Akiyama.

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Conflicts of interest

Y. Koyanagi, None; M. Akiyama, Endowed (NIDEK), Lecture fee (Novartis, Takeda, Mitsubishi Tanabe); K. M. Nishiguchi, None; Y. Momozawa, None; Y. Kamatani, None; S. Takata, None; C. Inai, None; Y. Iwasaki, None; M. Kumano, None; Y. Murakami, Grant (Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical's Founder, Bayer, Takeda Science Foundation), Lecture fee (Novartis, Bayer, Santen, AMO, Senju, Astellas); S. Komori, None; D. Gao, None; K. Kurata, None; K. Hosono, None; S. Ueno, Lecture fee (Novartis, TOMEY, NIDEK, HOYA, Santen, Nikon); Y. Hotta, None; A. Murakami, Grant, Financial support (Johnson & Johnson, Alcon, Otsuka, Kowa), Financial support (LION), Grant (IWAKI OPTICAL, Santen, AMO, Eisai, SEED, Senju, Novartis, Pfizer, HOYA, ROHTO); H. Terasaki, Grant, Honoraria for lecturing (Alcon, Bayer, Eizai, Novartis, Santen, Senju, Wakamoto, Otsuka, Kowa), Honoraria for lecturing, Non-financial support (ZEISS), Grant (AMO, HOYA), Honoraria for lecturing (Sanofi, AbbVie), Honoraria (ROHTO); Y. Wada, None; T. Nakazawa, Grant, Consultant fee, Lecture fee, Speaker fee (Santen, Senju), Grant, Lecture fee, Speaker fee (Topcon), Grant (NIDEK); T. Ishibashi, None; Y. Ikeda, Grant, Lecture fee, Consultant fee (HOYA), Grant (NIDEK); M. Kubo, None; K. Sonoda, None.

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Corresponding Author: Masato Akiyama

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Koyanagi, Y., Akiyama, M., Nishiguchi, K.M. et al. Regional differences in genes and variants causing retinitis pigmentosa in Japan. Jpn J Ophthalmol 65, 338–343 (2021).

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  • Genetics
  • Next-generation sequencing
  • Retinitis pigmentosa