CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes

Purpose: Ceramide kinase-like (CERKL) is a rarely reported gene in association with inherited retinal disease. This study aims to describe the genetic profile and phenotypic spectrum of CERKL-associated Retinal Degeneration (CERKL-RD) in Portugal. Design: Cross-sectional, multicenter cohort study Me...

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Main Authors: Catarina Pestana Aguiar, Lilianne Duarte, Célia Azevedo Soares, Pedro Marques-Couto, Sérgio Estrela-Silva, Ana Luísa Carvalho, João Pedro Marques
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:AJO International
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950253525000152
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Summary:Purpose: Ceramide kinase-like (CERKL) is a rarely reported gene in association with inherited retinal disease. This study aims to describe the genetic profile and phenotypic spectrum of CERKL-associated Retinal Degeneration (CERKL-RD) in Portugal. Design: Cross-sectional, multicenter cohort study Methods: Genotypic and phenotypic evaluation of 17 patients from 15 families from 3 Portuguese national health system health care providers. All patients were evaluated with multimodal retinal imaging (spectral domain optical coherence tomography, ultra-widefield color fundus photography and fundus autofluorescence). Genetic variants were classified in compliance with the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Results: The majority of patients were female (76.5 %), with a mean age of 49±17 years. The mean age at molecular diagnosis was 45.6 ± 16.1 years-old. Mean follow-up time was 60.6 ± 60.3 months. Most patients harbored the R257* variant in homozygosity, but with high intra- and interfamilial variability in the retinal phenotype. At the time of diagnosis, 41.2 % patients were already legally blind and this number raised to 52.9 % at the last available follow-up. Early macular involvement was a concerning characteristic observed in almost all cases. Conclusion: CERKL-RD in Portugal is predominantly associated with a nonsense variant, highlighting the potential role of nonsense suppression therapies for this population.
ISSN:2950-2535