Allelic Architecture and Clinical Spectrum of RP1-Associated Retinal Dystrophies in a Multicenter Korean Cohort.
11 affiliations
- 1Seoul National University College of Medicine, Seoul, South Korea.
- 2Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
- 3Keye Eye Center, Seoul, South Korea.
- 4Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.
- 5Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
- 6Institute of Vision Research, Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
- 7Institute of Vision Research, Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
- 8Department of Ophthalmology, Yeungnam University College of Medicine, Yeungnam University Medical Center, Daegu, South Korea.
- 9Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
- 10Department of Ophthalmology, Konkuk University College of Medicine, Seoul, South Korea.
- 11Department of Ophthalmology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.
Abstract
Purpose
To define the allelic architecture and phenotypic spectrum of RP1-associated retinal dystrophies in a large Korean cohort, emphasizing recurrent truncating alleles, phasing of linked variants, and mobile-element insertions (MEIs) underdetected by standard next-generation sequencing.Methods
This retrospective multicenter study included 143 patients with RP1-associated retinopathy sequenced at eight centers in Korea (2002-2025). Clinical findings, multimodal imaging, and electrophysiology were evaluated. Structural variants and allelic phase were assessed using an integrative genomics viewer-based soft-clipping review, Alu-PCR, and long-read whole-genome sequencing (lrWGS) in selected cases. Patients were classified as autosomal-dominant retinitis pigmentosa (AD-RP), autosomal-recessive RP (AR-RP), or recessive macular or cone(-rod) dystrophies.Results
Twenty-seven RP1 variants were identified, including nine novel alleles. All AD-RP cases were explained by seven exon 4 truncations within the dominant cluster. AR disease was dominated by three highly recurrent truncating alleles: c.4196del (p.Cys1399Leufs*5, carried by 32.2% of patients), the hypomorphic truncation c.5797C>T (p.Arg1933*, 30.8%), and c.6181del (p.Ile2061Serfs*12, 31.5%). The downstream missense variant c.6353G > A (p.Ser2118Asn) was consistently observed in cis with c.4196del, whereas c.4196del also occurred independently; this phase relationship was confirmed by lrWGS. The Alu insertion c.4052_4053ins328 (p.Tyr1352Alafs*9) was carried by 14% of patients. AR-RP presented earlier (mean onset 16.9 vs. 33.5 years, P < 0.001) and had poorer baseline worse-eye best-corrected visual acuity (logMAR, 1.05 vs. 0.44, P = 0.002) than AD-RP.Conclusions
This large ancestry-specific RP1-associated retinal dystrophy cohort refines the allelic landscape and underscores the importance of phasing and MEI-aware testing strategies, revealing broad phenotypic expansion to macular and cone(-rod) dystrophies and genotype-dependent severity profiles.
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BibTeX
@article{cho2026allelic,
title = {{Allelic Architecture and Clinical Spectrum of RP1-Associated Retinal Dystrophies in a Multicenter Korean Cohort.}},
author = {Yunnie Cho and Kwangsic Joo and Sohee Jeon and Eun Kyoung Lee and Jae Shin Song and Sungsoon Hwang and Jinu Han and Jay Jiyong Kwak and Suk Ho Byeon and Min Kim and Yong Joon Kim and Junwon Lee and Chang Ki Yoon and Min Sagong and Areum Jeong and Mirinae Kim and Ji Hye Lee and Hyewon Chung and Hyeong Min Kim and Dong Ho Park and Sang Jin Kim and Christopher Seungkyu Lee and Se Joon Woo},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.17},
url = {https://europepmc.org/article/MED/42847597},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Allelic Architecture and Clinical Spectrum of RP1-Associated Retinal Dystrophies in a Multicenter Korean Cohort.
AU - Yunnie Cho
AU - Kwangsic Joo
AU - Sohee Jeon
AU - Eun Kyoung Lee
AU - Jae Shin Song
AU - Sungsoon Hwang
AU - Jinu Han
AU - Jay Jiyong Kwak
AU - Suk Ho Byeon
AU - Min Kim
AU - Yong Joon Kim
AU - Junwon Lee
AU - Chang Ki Yoon
AU - Min Sagong
AU - Areum Jeong
AU - Mirinae Kim
AU - Ji Hye Lee
AU - Hyewon Chung
AU - Hyeong Min Kim
AU - Dong Ho Park
AU - Sang Jin Kim
AU - Christopher Seungkyu Lee
AU - Se Joon Woo
PY - 2026
DA - 2026/10/01
JO - Investigative ophthalmology & visual science
DO - 10.1167/iovs.67.12.17
UR - https://europepmc.org/article/MED/42847597
AB - Purpose To define the allelic architecture and phenotypic spectrum of RP1-associated retinal dystrophies in a large Korean cohort, emphasizing recurrent truncating alleles, phasing of linked variants, and mobile-element insertions (MEIs) underdetected by standard next-generation sequencing.Methods This retrospective multicenter study included 143 patients with RP1-associated retinopathy sequenced at eight centers in Korea (2002-2025). Clinical findings, multimodal imaging, and electrophysiology were evaluated. Structural variants and allelic phase were assessed using an integrative genomics viewer-based soft-clipping review, Alu-PCR, and long-read whole-genome sequencing (lrWGS) in selected cases. Patients were classified as autosomal-dominant retinitis pigmentosa (AD-RP), autosomal-recessive RP (AR-RP), or recessive macular or cone(-rod) dystrophies.Results Twenty-seven RP1 variants were identified, including nine novel alleles. All AD-RP cases were explained by seven exon 4 truncations within the dominant cluster. AR disease was dominated by three highly recurrent truncating alleles: c.4196del (p.Cys1399Leufs*5, carried by 32.2% of patients), the hypomorphic truncation c.5797C>T (p.Arg1933*, 30.8%), and c.6181del (p.Ile2061Serfs*12, 31.5%). The downstream missense variant c.6353G > A (p.Ser2118Asn) was consistently observed in cis with c.4196del, whereas c.4196del also occurred independently; this phase relationship was confirmed by lrWGS. The Alu insertion c.4052_4053ins328 (p.Tyr1352Alafs*9) was carried by 14% of patients. AR-RP presented earlier (mean onset 16.9 vs. 33.5 years, P < 0.001) and had poorer baseline worse-eye best-corrected visual acuity (logMAR, 1.05 vs. 0.44, P = 0.002) than AD-RP.Conclusions This large ancestry-specific RP1-associated retinal dystrophy cohort refines the allelic landscape and underscores the importance of phasing and MEI-aware testing strategies, revealing broad phenotypic expansion to macular and cone(-rod) dystrophies and genotype-dependent severity profiles.
SN - 0146-0404
SN - 1552-5783
ER -