Abstract
Purpose :
Inherited retinal degeneration (IRD) is a leading cause of bilateral blindness in youth worldwide and Leber congenital amaurosis (LCA) is one of the most early-onset and visual-threatening subtypes. Recently, the development of gene therapy shed a light for these patients. Since 2015, our team launched Taiwan inherited retinal degeneration project (TIP) and has devoted to provide clinical service for patients of IRD in Taiwan from clinical diagnosis, molecular analysis, and novel therapies. Here, we reported the genetic characteristics, genotype-phenotype correlation, and pilot treatment findings for Leber congenital amaurosis (LCA) from TIP experience.
Methods :
In TIP, 33 unrelated families (64 patients) of the 658 recruited IRD families from July 2015 to December 2021 were identified to have LCA. For each subject, a series of detailed ophthalmological examinations were performed including visual acuity, electroretinograms, fundus photography and autofluorescence imaging, and optical coherence tomography. Genomic DNA was extracted from peripheral blood samples and then sequenced by probe capture-based NGS approach of 233 IRD genes panel. The experimental methods and analysis pipeline for NGS data in this study was similar to our previous publication. (Chen et al., NPJ Genomic Medicine, 2021)
Results :
Twenty-three of the 33 familes (69.7%) got genetic diagnosis through capture-based NGS panel and RDH12 (9), CRB1 (5), CEP290 (3), and RPE65 (2) are most common genotypes identified in our LCA cohort. Patients of RDH12-related LCA typically showed prominant central lesion with variable peripheral pigmentary changes and a large portion of patients had c.505C>G and/or c.806C>G variants. Most of our patients of CRB1- and CEP290-related LCA has milder macular but more prominant peripheral degeneration. Noteworthy, none of our CEP290-related patients in this cohort owned IVS26 mutation. One of our RPE65-related patient has flecks in mid-periphery and, to our surprise, the flecks largely diappeared 6 months after gene therapy bilaterally.
Conclusions :
Here we reported our experience about genetic characteristics, genotype-phenotype correlation, and pilot treatment findings for Leber congenital amaurosis (LCA) in Taiwanese and hope this could help this field in clinical interpretation, genetic consultation, and future developement of gene therapy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.