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

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Abstract

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
Volume56
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

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Retinitis Pigmentosa
Databases
Population
Genes
Recessive Genes
Dominant Genes
Gene Frequency
Mutation

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. / Koyanagi, Yoshito; 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.

In: Journal of medical genetics, Vol. 56, No. 10, 01.10.2019, p. 662-670.

Research output: Contribution to journalArticle

Koyanagi, Y, Akiyama, M, Nishiguchi, KM, Momozawa, Y, Kamatani, Y, Takata, S, Inai, C, Iwasaki, Y, Kumano, M, Murakami, Y, Omodaka, K, Abe, T, Komori, S, Gao, D, Hirakata, T, Kurata, K, Hosono, K, Ueno, S, Hotta, Y, Murakami, A, Terasaki, H, Wada, Y, Nakazawa, T, Ishibashi, T, Ikeda, Y, Kubo, M & Sonoda, KH 2019, 'Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients', Journal of medical genetics, vol. 56, no. 10, pp. 662-670. https://doi.org/10.1136/jmedgenet-2018-105691
Koyanagi, Yoshito ; 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. / Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients. In: Journal of medical genetics. 2019 ; Vol. 56, No. 10. pp. 662-670.
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abstract = "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.",
author = "Yoshito Koyanagi and Masato Akiyama and Nishiguchi, {Koji M.} and Yukihide Momozawa and Yoichiro Kamatani and Sadaaki Takata and Chihiro Inai and Yusuke Iwasaki and Mikako Kumano and Yusuke Murakami and Kazuko Omodaka and Toshiaki Abe and Shiori Komori and Dan Gao and Toshiaki Hirakata and Kentaro Kurata and Katsuhiro Hosono and Shinji Ueno and Yoshihiro Hotta and Akira Murakami and Hiroko Terasaki and Yuko Wada and Toru Nakazawa and Tatsuro Ishibashi and Yasuhiro Ikeda and Michiaki Kubo and Sonoda, {Koh Hei}",
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TY - JOUR

T1 - Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients

AU - Koyanagi, Yoshito

AU - Akiyama, Masato

AU - Nishiguchi, Koji M.

AU - Momozawa, Yukihide

AU - Kamatani, Yoichiro

AU - Takata, Sadaaki

AU - Inai, Chihiro

AU - Iwasaki, Yusuke

AU - Kumano, Mikako

AU - Murakami, Yusuke

AU - Omodaka, Kazuko

AU - Abe, Toshiaki

AU - Komori, Shiori

AU - Gao, Dan

AU - Hirakata, Toshiaki

AU - Kurata, Kentaro

AU - Hosono, Katsuhiro

AU - Ueno, Shinji

AU - Hotta, Yoshihiro

AU - Murakami, Akira

AU - Terasaki, Hiroko

AU - Wada, Yuko

AU - Nakazawa, Toru

AU - Ishibashi, Tatsuro

AU - Ikeda, Yasuhiro

AU - Kubo, Michiaki

AU - Sonoda, Koh Hei

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

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U2 - 10.1136/jmedgenet-2018-105691

DO - 10.1136/jmedgenet-2018-105691

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