TY - JOUR
T1 - Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases
AU - Goto, Kensuke
AU - Koyanagi, Yoshito
AU - Akiyama, Masato
AU - Murakami, Yusuke
AU - Fukushima, Masatoshi
AU - Fujiwara, Kohta
AU - Iijima, Hanae
AU - Yamaguchi, Mitsuyo
AU - Endo, Mikiko
AU - Hashimoto, Kazuki
AU - Ishizu, Masataka
AU - Hirakata, Toshiaki
AU - Mizobuchi, Kei
AU - Takayama, Masakazu
AU - Ota, Junya
AU - Sajiki, Ai Fujita
AU - Kominami, Taro
AU - Ushida, Hiroaki
AU - Fujita, Kosuke
AU - Kaneko, Hiroki
AU - Ueno, Shinji
AU - Hayashi, Takaaki
AU - Terao, Chikashi
AU - Hotta, Yoshihiro
AU - Murakami, Akira
AU - Kuniyoshi, Kazuki
AU - Kusaka, Shunji
AU - Wada, Yuko
AU - Abe, Toshiaki
AU - Nakazawa, Toru
AU - Ikeda, Yasuhiro
AU - Momozawa, Yukihide
AU - Sonoda, Koh Hei
AU - Nishiguchi, Koji M.
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2024.
PY - 2024/6/20
Y1 - 2024/6/20
N2 - 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.
AB - 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.
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U2 - 10.1136/jmg-2023-109750
DO - 10.1136/jmg-2023-109750
M3 - Article
C2 - 38499336
AN - SCOPUS:85188649587
SN - 0022-2593
VL - 61
SP - 613
EP - 620
JO - Journal of medical genetics
JF - Journal of medical genetics
IS - 7
ER -