%0 Journal Article
%T Disease-specific variant interpretation highlighted the genetic findings in 2325 Japanese patients with retinitis pigmentosa and allied diseases.
%A Goto K
%A Koyanagi Y
%A Akiyama M
%A Murakami Y
%A Fukushima M
%A Fujiwara K
%A Iijima H
%A Yamaguchi M
%A Endo M
%A Hashimoto K
%A Ishizu M
%A Hirakata T
%A Mizobuchi K
%A Takayama M
%A Ota J
%A Sajiki AF
%A Kominami T
%A Ushida H
%A Fujita K
%A Kaneko H
%A Ueno S
%A Hayashi T
%A Terao C
%A Hotta Y
%A Murakami A
%A Kuniyoshi K
%A Kusaka S
%A Wada Y
%A Abe T
%A Nakazawa T
%A Ikeda Y
%A Momozawa Y
%A Sonoda KH
%A Nishiguchi KM
%J J Med Genet
%V 61
%N 7
%D 2024 Jun 20
%M 38499336
%F 5.941
%R 10.1136/jmg-2023-109750
%X 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.
CONCLUSIONS: 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.