Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases

Kensuke Goto, Yoshito Koyanagi, Masato Akiyama, Yusuke Murakami, Masatoshi Fukushima, Kohta Fujiwara, Hanae Iijima, Mitsuyo Yamaguchi, Mikiko Endo, Kazuki Hashimoto, Masataka Ishizu, Toshiaki Hirakata, Kei Mizobuchi, Masakazu Takayama, Junya Ota, Ai Fujita Sajiki, Taro Kominami, Hiroaki Ushida, Kosuke Fujita, Hiroki KanekoShinji Ueno, Takaaki Hayashi, Chikashi Terao, Yoshihiro Hotta, Akira Murakami, Kazuki Kuniyoshi, Shunji Kusaka, Yuko Wada, Toshiaki Abe, Toru Nakazawa, Yasuhiro Ikeda, Yukihide Momozawa, Koh Hei Sonoda, Koji M. Nishiguchi

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Background As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases. Methods We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines. Results A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases. Conclusion A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies.

本文言語英語
ページ(範囲)613-620
ページ数8
ジャーナルJournal of medical genetics
61
7
DOI
出版ステータス出版済み - 6月 20 2024

!!!All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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