Yoshito Koyanagi1,2, Masato Akiyama3,4,5, Koji M Nishiguchi6, Yukihide Momozawa7, Yoichiro Kamatani2,8, Sadaaki Takata7, Chihiro Inai7, Yusuke Iwasaki7, Mikako Kumano1, Yusuke Murakami1, Shiori Komori9, Dan Gao10, Kentaro Kurata11, Katsuhiro Hosono11, Shinji Ueno9, Yoshihiro Hotta11, Akira Murakami10, Hiroko Terasaki9, Yuko Wada12, Toru Nakazawa6,13, Tatsuro Ishibashi1, Yasuhiro Ikeda1,14, Michiaki Kubo15, Koh-Hei Sonoda1. 1. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 2. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan. 3. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. akiyamam@eye.med.kyushu-u.ac.jp. 4. Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan. akiyamam@eye.med.kyushu-u.ac.jp. 5. Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. akiyamam@eye.med.kyushu-u.ac.jp. 6. Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. 7. Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan. 8. Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan. 9. Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 10. Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, Japan. 11. Department of Ophthalmology, Hamamatsu University School of Medicine, Shizuoka, Japan. 12. Yuko WADA Eye Clinic, Sendai, Japan. 13. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan. 14. Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. 15. RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Abstract
PURPOSE: To investigate the regional differences in the genes and variants causing retinitis pigmentosa (RP) in Japan STUDY DESIGN: Retrospective multicenter study METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: To investigate the regional differences in the genes and variants causing retinitis pigmentosa (RP) in Japan STUDY DESIGN: Retrospective multicenter study METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: M Hayakawa; M Matsumura; N Ohba; M Matsui; K Fujiki; A Kanai; M Tamai; T Shiono; T Tokoro; Y Akazawa Journal: Jpn J Ophthalmol Date: 1993 Impact factor: 2.447
Authors: T Shiono; Y Hotta; M Noro; T Sakuma; M Tamai; M Hayakawa; T Hashimoto; K Fujiki; A Kanai; A Nakajima Journal: Jpn J Ophthalmol Date: 1992 Impact factor: 2.447
Authors: Xuan Cui; Hye Jin Kim; Chia-Hua Cheng; Laura A Jenny; Jose Ronaldo Lima de Carvalho; Ya-Ju Chang; Yang Kong; Chun-Wei Hsu; I-Wen Huang; Sara D Ragi; Chyuan-Sheng Lin; Xiaorong Li; Janet R Sparrow; Stephen H Tsang Journal: Hum Mol Genet Date: 2022-07-21 Impact factor: 5.121