CERKL-related inherited retinal dystrophy in a Brazilian cohort: genotype-phenotype correlation

The purpose of this study was to analyze the genotype-phenotype of CERKL-related inherited retinal dystrophy in an outpatient clinic. For the study, 2841 medical records of Brazilian patients with a diagnosis of an inherited retinal dystrophy (IRD) registered at Instituto de Genética Ocular, Brazil, between January 2006 and July 2025 were retrospectively reviewed and 52 patients from 50 unrelated families with a molecular diagnosis of an IRD related to the CERKL gene were selected. Clinical data and molecular tests results were analyzed for genotype-phenotype correlation. Most patients (50/52) presented with the cone rod dystrophy (CORD) and two patients presented with the macular dystrophy (MD) phenotype. Age of presenting symptoms ranged from early childhood (7 years old) to adulthood (40 years old). BCVA Snellen measured at the first visit ranged from 20/25 to light perception, corresponding to 0.1 to 2.7 in log MAR visual acuity. Visual acuity data according to disease duration at the first visit of 37 double null (DN) alleles patients disclosed a Pearson coefficient R² of 0.315 for the right eye and 0.405 for the left eye, respectively. A highly significant association between disease duration and visual acuity loss was found suggesting consistent and predictable visual deterioration in patients with complete CERKL loss-of-function over time. Twenty-four different variants described in the CERKL gene were identified. The c.847C>T (p.Arg283) nonsense variant in exon 6 was the most common variant in this cohort, identified in 24 homozygous out of 52 individuals and in 12 compound heterozygous. The phenotype of CERKL-related IRD is CORD with an early age of presentation and fast decrease in visual acuity. In addition to OMIM classifying this gene as an retinitis pigmentosa IRD, we believe CERKL has CORD phenotype, in concordance with evidence described in the literature.