ArticleHuman molecular genetics2011
Decreased catalytic activity and altered activation properties of PDE6C mutants associated with autosomal recessive achromatopsia.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Expanding phenotypic and genotypic spectrum of PDE6C-associated retinal disorders.Eye (London, England) · 2026Article
- Progressive cone dystrophy in PDE6C-associated achromatopsia with a likely pathogenic variant and a VUS.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives.Genes · 2025Review
- Coevolving residues distant from the ligand binding site are involved in GAF domain function.Communications chemistry · 2025Article
- Structural and functional dynamics of human cone cGMP-phosphodiesterase important for photopic vision.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Onset and Progression of Disease in Nonhuman Primates With PDE6C Cone Disorder.Investigative ophthalmology & visual science · 2024Article
- Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia.BMC medical genomics · 2024Article
- Dyschromatopsia: a comprehensive analysis of mechanisms and cutting-edge treatments for color vision deficiency.Frontiers in neuroscience · 2024Review
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Prenylation is essential for the enrichment of cone phosphodiesterase-6 (PDE6) in outer segments and efficient cone phototransduction.Human molecular genetics · 2023Article
- cGMP Signaling in Photoreceptor Degeneration.International journal of molecular sciences · 2023Review
- Article
- High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs.International journal of molecular sciences · 2023Article
- Gene losses in the common vampire bat illuminate molecular adaptations to blood feeding.Science advances · 2022Article
- Structural Analysis of the Regulatory GAF Domains of cGMP Phosphodiesterase Elucidates the Allosteric Communication Pathway.Journal of molecular biology · 2020Article
- PDE6C: Novel Mutations, Atypical Phenotype, and Differences Among Children and Adults.Investigative ophthalmology & visual science · 2020Article
- Long-Term Investigation of Retinal Function in Patients with Achromatopsia.Investigative ophthalmology & visual science · 2020Article
- Genotypes and phenotypes of genes associated with achromatopsia: A reference for clinical genetic testing.Molecular vision · 2020Article
- Deep Phenotyping of PDE6C-Associated Achromatopsia.Investigative ophthalmology & visual science · 2019Article
- Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory Pγ subunit of phosphodiesterase 6.The Journal of biological chemistry · 2019Article
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Authors and funding
13 authors at 9 institutions in 7 countries.
Funding
Abstract
Mutations in the gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase (PDE6C) have been recently reported in patients with autosomal recessive inherited achromatopsia (ACHM) and early-onset cone photoreceptor dysfunction. Here we present the results of a comprehensive study on PDE6C mutations including the mutation spectrum, its prevalence in a large cohort of ACHM/cone dysfunction patients, the clinical phenotype and the functional characterization of mutant PDE6C proteins. Twelve affected patients from seven independent families segregating PDE6C mutations were identified in our total patient cohort of 492 independent families. Eleven different PDE6C mutations were found including two nonsense mutations, three mutations affecting transcript splicing as shown by minigene assays, one 1 bp-insertion and five missense mutations. We also performed a detailed functional characterization of six missense mutations applying the baculovirus system to express recombinant mutant and wildtype chimeric PDE6C/PDE5 proteins in Sf9 insect cells. Purified proteins were analyzed using Western blotting, phosphodiesterase (PDE) activity measurements as well as inhibition assays by zaprinast and Pγ. Four of the six PDE6C missense mutations led to baseline PDE activities and most likely represent functional null alleles. For two mutations, p.E790K and p.Y323N, we observed reduction in PDE activity of approximately 60% and 80%, respectively. We also observed differences for Pγ inhibition. The p.E790K mutant, with an IC₅₀ value of 2.7 nm is 20.7-fold more sensitive for Pγ inhibition, whereas the p.Y323N mutant with an IC₅₀ of 158 nm is 3-fold less sensitive when compared with the wildtype control.
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