ArticleAmerican journal of human genetics2004
Mutation of CERKL, a novel human ceramide kinase gene, causes autosomal recessive retinitis pigmentosa (RP26).
Article in American journal of human genetics, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 194 citations in OpenAlex.
- Trial
- Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland.Human genetics · 2015Trial
- Retina-specific long non-coding RNAs associated with inherited retinal disease genes.Cellular and molecular life sciences : CMLS · 2026Article
- A nonpigmented retinal pigment epithelium adenoma with retinitis pigmentosa:A case report.American journal of ophthalmology case reports · 2026Article
- Lipid ciliology: specialized ciliary membrane lipids in physiology and disease.Frontiers in cell and developmental biology · 2026Review
- Article
- Genome-wide association analyses reveal susceptibility variants linked to Parkinson's disease in the South African population using inferred global and local ancestry.medRxiv : the preprint server for health sciences · 2025Article
- The genotype-phenotype association of retinitis pigmentosa in a Chinese population: Analysis of three new cases and literature review.Molecular vision · 2025Review
- Review
- Avidity sequencing of whole genomes from retinal degeneration pedigrees identifies causal variants.PloS one · 2024Article
- Alternative RNA Splicing in the Retina: Insights and Perspectives.Cold Spring Harbor perspectives in medicine · 2023Review
- Exacerbated response to oxidative stress in the Retinitis Pigmentosa CerklRedox biology · 2023Article
- CERKL-Associated Retinal Dystrophy: Genetics, Phenotype, and Natural History.Ophthalmology. Retina · 2023Article
- Primary versus Secondary Elevations in Fundus Autofluorescence.International journal of molecular sciences · 2023Review
- Novel pathogenic3 Biotech · 2023Article
- Nationwide genetic analysis of more than 600 families with inherited eye diseases in Argentina.NPJ genomic medicine · 2023Article
- Article
- Oxidative Stress Implication in Retinal Diseases-A Review.Antioxidants (Basel, Switzerland) · 2022Review
- Ciliogenesis requires sphingolipid-dependent membrane and axoneme interaction.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life.Progress in retinal and eye research · 2022Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinitis pigmentosa (RP), the main cause of adult blindness, is a genetically heterogeneous disorder characterized by progressive loss of photoreceptors through apoptosis. Up to now, 39 genes and loci have been implicated in nonsyndromic RP, yet the genetic bases of >50% of the cases, particularly of the recessive forms, remain unknown. Previous linkage analysis in a Spanish consanguineous family allowed us to define a novel autosomal recessive RP (arRP) locus, RP26, within an 11-cM interval (17.4 Mb) on 2q31.2-q32.3. In the present study, we further refine the RP26 locus down to 2.5 Mb, by microsatellite and single-nucleotide polymorphism (SNP) homozygosity mapping. After unsuccessful mutational analysis of the nine genes initially reported in this region, a detailed gene search based on expressed-sequence-tag data was undertaken. We finally identified a novel gene encoding a ceramide kinase (CERKL), which encompassed 13 exons. All of the patients from the RP26 family bear a homozygous mutation in exon 5, which generates a premature termination codon. The same mutation was also characterized in another, unrelated, Spanish pedigree with arRP. Human CERKL is expressed in the retina, among other adult and fetal tissues. A more detailed analysis by in situ hybridization on adult murine retina sections shows expression of Cerkl in the ganglion cell layer. Ceramide kinases convert the sphingolipid metabolite ceramide into ceramide-1-phosphate, both key mediators of cellular apoptosis and survival. Ceramide metabolism plays an essential role in the viability of neuronal cells, the membranes of which are particularly rich in sphingolipids. Therefore, CERKL deficiency could shift the relative levels of the signaling sphingolipid metabolites and increase sensitivity of photoreceptor and other retinal cells to apoptotic stimuli. This is the first genetic report suggesting a direct link between retinal neurodegeneration in RP and sphingolipid-mediated apoptosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.