Dae Joong Ma1,2, Hyun-Seob Lee3, Kwangsoo Kim4, Seongmin Choi5, Insoon Jang5, Seo-Ho Cho5, Chang Ki Yoon1,6, Eun Kyoung Lee1,6, Hyeong Gon Yu7,8. 1. Retinal Degeneration Research Lab, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. 2. Department of Ophthalmology, Hallym University Kangnam Sacred Heart Hospital, Seoul, Republic of Korea. 3. Genomics Core Facility, Translational Research Institute, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. 4. Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Republic of Korea. 5. Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. 6. Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea. 7. Retinal Degeneration Research Lab, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. hgonyu@snu.ac.kr. 8. Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, Republic of Korea. hgonyu@snu.ac.kr.
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.
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.
Authors: Yuchen Lin; Christine L Xu; Gabriel Velez; Jing Yang; Akemi J Tanaka; Mark P Breazzano; Vinit B Mahajan; Janet R Sparrow; Stephen H Tsang Journal: Doc Ophthalmol Date: 2019-09-19 Impact factor: 2.379
Authors: Feng Wang; Hui Wang; Han-Fang Tuan; Duy H Nguyen; Vincent Sun; Vafa Keser; Sara J Bowne; Lori S Sullivan; Hongrong Luo; Ling Zhao; Xia Wang; Jacques E Zaneveld; Jason S Salvo; Sorath Siddiqui; Louise Mao; Dianna K Wheaton; David G Birch; Kari E Branham; John R Heckenlively; Cindy Wen; Ken Flagg; Henry Ferreyra; Jacqueline Pei; Ayesha Khan; Huanan Ren; Keqing Wang; Irma Lopez; Raheel Qamar; Juan C Zenteno; Raul Ayala-Ramirez; Beatriz Buentello-Volante; Qing Fu; David A Simpson; Yumei Li; Ruifang Sui; Giuliana Silvestri; Stephen P Daiger; Robert K Koenekoop; Kang Zhang; Rui Chen Journal: Hum Genet Date: 2013-10-24 Impact factor: 4.132
Authors: Sun Ho Lee; Hyeong Gon Yu; Jong Mo Seo; Sang Woong Moon; Jun Woong Moon; Sang Jin Kim; Hum Chung Journal: J Korean Med Sci Date: 2010-05-24 Impact factor: 2.153
Authors: Kirk A J Stephenson; Julia Zhu; Adrian Dockery; Laura Whelan; Tomás Burke; Jacqueline Turner; James J O'Byrne; G Jane Farrar; David J Keegan Journal: Int J Mol Sci Date: 2022-01-17 Impact factor: 5.923
Authors: Beau J Fenner; Tien-En Tan; Amutha Veluchamy Barathi; Sai Bo Bo Tun; Sia Wey Yeo; Andrew S H Tsai; Shu Yen Lee; Chui Ming Gemmy Cheung; Choi Mun Chan; Jodhbir S Mehta; Kelvin Y C Teo Journal: Front Genet Date: 2022-01-07 Impact factor: 4.599
Authors: Jin Ha Kim; Jung Woo Han; Eun Woo Choi; Ji Hong Bang; Hee Jeong Shin; Mi-Ae Jang; Jong-Young Lee; Jeong Nam Choi; Hun Soo Chang; Tae Kwann Park Journal: J Korean Med Sci Date: 2022-01-17 Impact factor: 2.153