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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Elsevier
2025-07-01
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| Series: | AJO International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950253525000152 |
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| author | Catarina Pestana Aguiar Lilianne Duarte Célia Azevedo Soares Pedro Marques-Couto Sérgio Estrela-Silva Ana Luísa Carvalho João Pedro Marques |
| author_facet | Catarina Pestana Aguiar Lilianne Duarte Célia Azevedo Soares Pedro Marques-Couto Sérgio Estrela-Silva Ana Luísa Carvalho João Pedro Marques |
| author_sort | Catarina Pestana Aguiar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-29a30f004d6047efaf9859cb68ae50d6 |
| institution | Kabale University |
| issn | 2950-2535 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | AJO International |
| spelling | doaj-art-29a30f004d6047efaf9859cb68ae50d62025-08-20T03:26:35ZengElsevierAJO International2950-25352025-07-012210011210.1016/j.ajoint.2025.100112CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypesCatarina Pestana Aguiar0Lilianne Duarte1Célia Azevedo Soares2Pedro Marques-Couto3Sérgio Estrela-Silva4Ana Luísa Carvalho5João Pedro Marques6Ophthalmology Department, Hospital de São Sebastião, Unidade Local de Saúde Entre o Douro e Vouga, Santa Maria da Feira, PortugalOphthalmology Department, Hospital de São Sebastião, Unidade Local de Saúde Entre o Douro e Vouga, Santa Maria da Feira, PortugalGenetics Department, Centro de Genética Médica Jacinto Magalhães, Unidade Saúde Local de Santo António, Porto, Portugal; Unit for Multidisciplinary Research in Biomedicine, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; Medical Sciences Department, Aveiro University, Aveiro, PortugalOphthalmology Department, Hospital de São João, Unidade Local de Saúde São João, Porto, PortugalOphthalmology Department, Hospital de São João, Unidade Local de Saúde São João, Porto, Portugal; Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, PortugalMedical Genetics Department, Hospital Pediátrico de Coimbra, Unidade Local de Saúde de Coimbra, Coimbra, Portugal; Clinical and Academic Center of Coimbra (CACC), Unidade Local de Saúde de Coimbra, Coimbra, Portugal; Clínica Universitária de Genética, Faculdade de Medicina, Universidade de Coimbra (FMUC), Coimbra, PortugalClinical and Academic Center of Coimbra (CACC), Unidade Local de Saúde de Coimbra, Coimbra, Portugal; Ophthalmology Department, Hospitais da Universidade de Coimbra, Unidade Local de Saúde Coimbra, Coimbra, Portugal; Corresponding author at: Ophthalmology Department, Unidade Local de Saúde de Coimbra (ULS Coimbra), Praceta Professor Mota Pinto, 3004-561 Coimbra, Portugal.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.http://www.sciencedirect.com/science/article/pii/S2950253525000152Retinitis pigmentosaInherited retinal diseaseCERKLNonsense variantOphthalmic genetics |
| spellingShingle | Catarina Pestana Aguiar Lilianne Duarte Célia Azevedo Soares Pedro Marques-Couto Sérgio Estrela-Silva Ana Luísa Carvalho João Pedro Marques CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes AJO International Retinitis pigmentosa Inherited retinal disease CERKL Nonsense variant Ophthalmic genetics |
| title | CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes |
| title_full | CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes |
| title_fullStr | CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes |
| title_full_unstemmed | CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes |
| title_short | CERKL-associated retinal degeneration in Portugal: Mutational spectrum and retinal phenotypes |
| title_sort | cerkl associated retinal degeneration in portugal mutational spectrum and retinal phenotypes |
| topic | Retinitis pigmentosa Inherited retinal disease CERKL Nonsense variant Ophthalmic genetics |
| url | http://www.sciencedirect.com/science/article/pii/S2950253525000152 |
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