Highly efficient capture approach for the identification of diverse inherited retinal disorders

Hsiao Jung Kao, Ting Yi Lin, Feng Jen Hsieh, Jia Ying Chien, Erh Chan Yeh, Wan Jia Lin, Yi Hua Chen, Kai Hsuan Ding, Yu Yang, Sheng Chu Chi, Ping Hsing Tsai, Chih Chien Hsu, De Kuang Hwang, Hsien Yang Tsai, Mei Ling Peng, Shi Huang Lee, Siu Fung Chau, Chen Yu Chen, Wai Man Cheang, Shih Jen ChenPui Yan Kwok*, Shih Hwa Chiou*, Mei Yeh Jade Lu*, Shun Ping Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

Original languageEnglish
Article number4
Journalnpj Genomic Medicine
Volume9
Issue number1
DOIs
StatePublished - Dec 2024

Fingerprint

Dive into the research topics of 'Highly efficient capture approach for the identification of diverse inherited retinal disorders'. Together they form a unique fingerprint.

Cite this