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Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy
  1. Marina Riera1,2,
  2. Víctor Abad-Morales1,2,
  3. Rafael Navarro2,3,
  4. Sheila Ruiz-Nogales1,2,
  5. Pilar Méndez-Vendrell1,2,
  6. Borja Corcostegui2,3,
  7. Esther Pomares1,2
  1. 1 Genetics, Institut de Microcirurgia Ocular, Barcelona, Spain
  2. 2 Fundació de Recerca de l'Institut de Microcirurgia Ocular, Barcelona, Spain
  3. 3 Retina, Institut de Microcirurgia Ocular, Barcelona, Spain
  1. Correspondence to Dr Marina Riera, Genetics, Institut de Microcirurgia Ocular, Barcelona 08035, Spain; genetica.riera{at}; Dr Esther Pomares, Genetics, Institut de Microcirurgia Ocular, Barcelona 08035, Spain; pomares{at}


Purpose This study aimed to identify the underlying genetic cause(s) of inherited retinal dystrophy (IRD) in 12 families of Kuwaiti origin affected by macular dystrophy and four Spanish patients affected by retinitis pigmentosa (RP).

Methods Clinical diagnoses were based on standard ophthalmic evaluations (best-corrected visual acuity, retinography, fundus autofluorescence imaging, optical coherence tomography, electroretinography and visual field tests). Panel-based whole exome sequencing was used to simultaneously analyse 224 IRD genes in one affected member of each family. The putative causative variants were confirmed by Sanger sequencing and cosegregation analyses. Haplotype analysis was performed using single nucleotide polymorphisms.

Results A homozygous missense mutation c.606C>A (p.Asp202Glu) in RP1 was found to be the molecular cause of IRD in all 12 families from Kuwait. These patients exhibited comparable symptoms, including progressive decline in visual acuity since adolescence. Fundus autofluorescence images revealed bilateral macular retinal pigment epithelium disturbances, with neither perimacular flecks nor peripheral alterations. A shared haplotype spanning at least 1.1 Mb was identified in all families, suggesting a founder effect. Furthermore, RP1 variants involving nonsense and/or frameshifting mutations (three of them novel) were identified in three Spanish autosomal-recessive RP families and one dominant RP pedigree.

Conclusion This study describes, for the first time, a macular dystrophy phenotype caused by an RP1 mutation; establishing a new genotype-phenotype correlation in this gene, expanding its mutation spectrum and further highlighting the clinical heterogeneity associated with IRD.

  • degeneration
  • genetics
  • macula
  • retina

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  • Contributors MR, VA-M, RN and EP designed the study and experiments. RN and BC diagnosed all patients at clinical level and collected phenotypic data. MR, VA-M, SR-N and PM. performed the experimental analyses. MR, RN and EP wrote the manuscript and prepared all the figures. All authors approved the final version to be published.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.

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