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.

Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina

“…2 The mean age at genetic testing in Argentina was similar to a large cohort in USA (36.5 years versus 37.3), 40 and younger than other groups in Asia. 37,41 The percentage of individuals with positive family history was similar to other cohorts as well, with consistent no signi cant age differences between positive and negative family history subcohorts. 37,41 Still, there was an 8-yeardifference between mean age of onset and diagnosis, and a further 14-years-gap until genetic testing.…”

Autosomal Dominant Retinitis Pigmentosa–Associated TOPORS Protein Truncating Variants Are Exclusively Located in the Region of Amino Acid Residues 807 to 867

“…Based on the HGMD database (as of January 2021), LOVD database (as of December 2021), and PubMed search (as of January 2022), 17 heterozygous truncating variants of TOPORS were reported to be causative for autosomal dominant retinopathy in 47 families, including 42 families with typical RP and five families with unclassified retinal dystrophy. 4 – 16 , 31 – 45 All except one variant were distributed in exon 3, which is the last exon of TOPORS . These variants were clustered in a specific region from coding residues 807 to 867 downstream of the SR/RS domain ( Fig.…”

Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa

“…The CHM mutation was reported in about 1% of patients with inherited retinal disorder in WES. 15 16 The pathogenetic mechanism of choroideremia has not yet to be fully elucidated, and the disease progresses very slowly, making early diagnosis difficult. Retinal thickening occurs in the earliest disease stage, although normal lamination is maintained.…”