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

Abstract

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.