Allelic Architecture and Clinical Spectrum of RP1-Associated Retinal Dystrophies in a Multicenter Korean Cohort.

RP1

RP1 exon 4 truncations in dominant forms; recurrent truncating alleles, including an Alu insertion, in recessive forms

This retrospective multicentre study includes 143 Korean patients with RP1-associated retinopathy sequenced at eight centres between 2002 and 2025, with structural variant and phase assessment using soft-clipping review, Alu-PCR and long-read WGS in selected cases. Twenty-seven RP1 variants were identified, nine of them novel; all dominant retinitis pigmentosa cases were explained by seven exon 4 truncations, whereas recessive disease was dominated by three recurrent truncating alleles: c.4196del (p.Cys1399LeufsTer5, 32.2% of patients), the hypomorphic truncation c.5797C>T (p.Arg1933Ter, 30.8%) and c.6181del (p.Ile2061SerfsTer12, 31.5%). The missense c.6353G>A (p.Ser2118Asn) was found in cis with c.4196del, a phase confirmed by long-read WGS, and the Alu insertion c.4052_4053ins328 (p.Tyr1352AlafsTer9) was carried by 14% of patients. Recessive forms started earlier than dominant ones (mean onset 16.9 vs 33.5 years, p < 0.001) with poorer baseline visual acuity, and the spectrum extended to macular and cone(-rod) dystrophies.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The Alu insertion carried by 14% of patients is the warning sign: a short-read exome/genome pipeline without mobile element detection misses a substantial share of RP1 diagnoses in this population. Phasing c.4196del with p.Ser2118Asn avoids wrongly counting two distinct alleles in a recessive patient. These allele frequencies are specific to a Korean population and do not transfer as such elsewhere.

Analysis by Dr Thibaut Benquey