Allelic Architecture and Clinical Spectrum of RP1 -Associated Retinal Dystrophies in a Multicenter Korean Cohort
Year: 2026
Type: article
Study design: Observational Study
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.
Authors: Yunnie Cho, Kwangsic Joo, Sohee Jeon, Eun Kyoung Lee, Jae Shin Song, Sungsoon Hwang, Jinu Han, Jay Jiyong Kwak, Suk Ho Byeon, Min Kim, Yong Joon Kim, Junwon Lee, Chang Ki Yoon, Min Sagong, Areum Jeong, Mirinae Kim, Ji Hye Lee, Hyewon Chung, Hyeong Min Kim, Dong Ho Park, Sang Jin Kim, Christopher Seungkyu Lee, Se Joon Woo
Institutions: Seoul National University, Seoul National University Bundang Hospital, Seoul National University Hospital, Samsung Medical Center, Sungkyunkwan University, Yonsei University, Severance Hospital, The Catholic University of Korea Seoul St. Mary's Hospital, Catholic University of Korea, Gangnam Severance Hospital, Yeungnam University Medical Center, Yeungnam University College, Yeungnam University, Konkuk University, Konkuk University Medical Center, Kyungpook National University Hospital, Kyungpook National University
Language: English
Subfield: Ophthalmology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,850
OpenAlex ID: W7220996938