한빛사논문
- 조회337
Dongheon Surl, MD1; Dongju Won, MD2; Seung-Tae Lee, MD, PhD2; Christopher Seungkyu Lee, MD, PhD3; Junwon Lee, MD, PhD1; Hyun Taek Lim, MD, PhD4; Seung Ah Chung, MD, PhD5; Won Kyung Song, MD, PhD6; Min Kim, MD, PhD1; Sung Soo Kim, MD, PhD3; Saeam Shin, MD, PhD2; Jong Rak Choi, MD, PhD2; Riccardo Sangermano, PhD7; Suk Ho Byeon, MD, PhD3; Kinga M. Bujakowska, PhD7; Jinu Han, MD, PhD1,7
1Institute of Vision Research, Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
2Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
3Institute of Vision Research, Severance Hospital, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea
4Seoul Orthopia Eye Clinic, Seoul, South Korea
5Department of Ophthalmology, Ajou University School of Medicine, Suwon, South Korea
6Gangnam Yonsei Eye Clinic, Seoul, South Korea
7Ocular Genomics Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston
Drs Surl, Won, and S.-T. Lee contributed equally as first authors.
Corresponding Author: Kinga Bujakowska, PhD, Jinu Han, MD
Abstract
Importance: Despite advances in next-generation sequencing (NGS), a significant proportion of patients with inherited retinal disease (IRD) remain undiagnosed after initial genetic testing. Exome sequencing (ES) reanalysis in the clinical setting has been suggested as one method for improving diagnosis of IRD.
Objective: To investigate the association of clinician-led reanalysis of ES data, which incorporates updated clinical information and comprehensive bioinformatic analysis, with the diagnostic yield in a cohort of patients with IRDs in Korea.
Design, setting, and participants: This was a multicenter prospective cohort study involving 264 unrelated patients with IRDs, conducted in Korea between March 2018 and February 2020. Comprehensive ophthalmologic examinations and ES analyses were performed, and ES data were reanalyzed by an IRD specialist for single nucleotide variants, copy number variants, mobile element insertions, and mitochondrial variants. Data were analyzed from March to July 2023.
Main outcomes and measures: Diagnostic rate of conventional bioinformatic analysis and clinician-driven ES reanalysis.
Results: A total of 264 participants (151 [57.2%] male; mean [SD] age at genetic testing, 33.6 [18.9] years) were enrolled, including 129 patients (48.9%) with retinitis pigmentosa and 26 patients (9.8%) with Stargardt disease or macular dystrophy. Initial bioinformatic analysis diagnosed 166 patients (62.9%). Clinician-driven reanalysis identified the molecular cause of diseases in an additional 22 patients, corresponding to an 8.3-percentage point increase in diagnostic rate. Key factors associated with new molecular diagnoses included clinical phenotype updates (4 patients) and detection of previously overlooked variation, such as structural variants (9 patients), mitochondrial variants (3 patients), filtered or not captured variants (4 patients), and noncanonical splicing variants (2 patients). Among the 22 patients, variants in 7 patients (31.8%) were observed in the initial analysis but not reported to patients, while those in the remaining 15 patients (68.2%) were newly detected by the ES reanalysis.
Conclusions and relevance: In this cohort study, clinician-centered reanalysis of ES data was associated with improved molecular diagnostic yields in patients with IRD. This approach is important for uncovering missed genetic causes of retinal disease.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-06-03)
- 국내(교신)+국외 연구진
- 의약학 > 유전 및 유전체의학
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