Whole-exome sequencing in 168 Korean patients with inherited retinal degeneration

Abstract

Background: To date, no genetic analysis of inherited retinal disease (IRD) using whole-exome sequencing (WES) has been conducted in a large-scale Korean cohort. The aim of this study was to characterise the genetic profile of IRD patients in Korea using WES.

Methods: We performed comprehensive molecular testing in 168 unrelated Korean IRD patients using WES. The potential pathogenicity of candidate variants was assessed using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology variant interpretation guidelines, in silico prediction tools, published literature, and compatibility with known phenotypes or inheritance patterns.

Results: Causative variants were detected in 86/168 (51.2%) IRD patients, including 58/107 (54.2%) with retinitis pigmentosa, 7/15 (46.7%) with cone and cone-rod dystrophy, 2/3 (66.6%) with Usher syndrome, 1/2 (50.0%) with congenital stationary night blindness, 2/2 (100.0%) with Leber congenital amaurosis, 1/1 (100.0%) with Bietti crystalline dystrophy, 1/1 (100.0%) with Joubert syndrome, 9/10 (90.0%) with Stargardt macular dystrophy, 1/10 (10.0%) with vitelliform macular dystrophy, 1/11 (9.1%) with other forms of macular dystrophy, and 3/4 (75.0%) with choroideraemia. USH2A, ABCA4, and EYS were the most common causative genes associated with IRD. For retinitis pigmentosa, variants of USH2A and EYS were the most common causative gene mutations.

Conclusions: This study demonstrated the distribution of causative genetic mutations in Korean IRD patients. The data will serve as a reference for future genetic screening and development of treatment modalities for Korean IRD patients.

Keywords: Inherited retinal degeneration; Retinitis pigmentosa; Whole-exome sequencing.

Fig. 1

USH2A and ABCA4 mutations were the most common causative variants among inherited retinal degeneration patients. All data are from the present study

Fig. 2

The number of detected pathogenic mutations for each disease phenotype. BBS Bardet–Biedl syndrome, Bietti Bietti crystalline dystrophy, CHM choroideraemia, CSNB congenital stationary night blindness, CORD cone and cone-rod dystrophy, Joubert Joubert syndrome, LCA Leber congenital amaurosis, MD other macular dystrophy, NCMD North Carolina macular dystrophy, RP retinitis pigmentosa, STGD Stargardt macular dystrophy, Usher Usher syndrome, VMD vitelliform macular dystrophy

Fig. 3

Clinical phenotypes of case 55, who carries a hemizygous mutation in the CHM gene. a, b Colour fundus photograph. c, d Optical coherence tomography images. e, f Vision field diagram. g Electroretinography recording

Fig. 4

Clinical phenotypes of case 147, who carries compound heterozygous mutations in the CYP4V2 gene. a, b Colour fundus photographs taken at the time of genetic analysis. c, d Colour fundus photographs from 9 years prior to the study

Fig. 5

Percentages of causative genes identified in 58 retinitis pigmentosa patients. Mutations in EYS and USH2A were the most common in the population (a). The proportion of causative genes based on inheritance pattern is shown in b. All data are from the present study