ArticleThe Journal of clinical investigation2018
Accessory heterozygous mutations in cone photoreceptor CNGA3 exacerbate CNG channel-associated retinopathy.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Comprehensive functional splicing analysis of non-canonical CNGB3 variants using in vitro minigene splice assays.The Journal of pathology · 2025Article
- Expansion of the ABCA4-Associated Retinopathy Spectrum: Severe Variants Can be Associated With Early-Onset Severe Retinal Dystrophy.Investigative ophthalmology & visual science · 2025Article
- Monogenic Retinal Diseases Associated With Genes Encoding Phototransduction Proteins: A Review.Clinical & experimental ophthalmology · 2025Review
- Review
- Uncovering recessive alleles in rare Mendelian disorders by genome sequencing of 174 individuals with monoallelic pathogenic variants.European journal of human genetics : EJHG · 2025Article
- The BXD32 Mouse: A High-Fidelity Model of Chronic Retinal Inflammation and Photoreceptor Degeneration.Advances in experimental medicine and biology · 2025Article
- Infantile Nystagmus Syndrome-Associated Inherited Retinal Diseases: Perspectives from Gene Therapy Clinical Trials.Life (Basel, Switzerland) · 2024Review
- The co-occurrence of genetic variants in the TYR and OCA2 genes confers susceptibility to albinism.Nature communications · 2024Article
- Gene Therapy for Achromatopsia.International journal of molecular sciences · 2024Review
- Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes.Biomolecules · 2024Article
- Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels.Channels (Austin, Tex.) · 2023Review
- Article
- Systematic analysis of CNGA3 splice variants identifies different mechanisms of aberrant splicing.Scientific reports · 2023Article
- Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.Biomedicines · 2023Review
- Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases.Human mutation · 2022Article
- Rare and common variants in ROM1 and PRPH2 genes trans-modify Stargardt/ABCA4 disease.PLoS genetics · 2022Article
- dCas9-VPR-mediated transcriptional activation of functionally equivalent genes for gene therapy.Nature protocols · 2022Review
- Structure of the human cone photoreceptor cyclic nucleotide-gated channel.Nature structural & molecular biology · 2022Article
- Achromatopsia: Genetics and Gene Therapy.Molecular diagnosis & therapy · 2022Review
- Chronic Proinflammatory Signaling Accelerates the Rate of Degeneration in a Spontaneous Polygenic Model of Inherited Retinal Dystrophy.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
34 authors at 12 institutions in 6 countries.
Funding
Abstract
Mutations in CNGA3 and CNGB3, the genes encoding the subunits of the tetrameric cone photoreceptor cyclic nucleotide-gated ion channel, cause achromatopsia, a congenital retinal disorder characterized by loss of cone function. However, a small number of patients carrying the CNGB3/c.1208G>A;p.R403Q mutation present with a variable retinal phenotype ranging from complete and incomplete achromatopsia to moderate cone dysfunction or progressive cone dystrophy. By exploring a large patient cohort and published cases, we identified 16 unrelated individuals who were homozygous or (compound-)heterozygous for the CNGB3/c.1208G>A;p.R403Q mutation. In-depth genetic and clinical analysis revealed a co-occurrence of a mutant CNGA3 allele in a high proportion of these patients (10 of 16), likely contributing to the disease phenotype. To verify these findings, we generated a Cngb3R403Q/R403Q mouse model, which was crossbred with Cnga3-deficient (Cnga3-/-) mice to obtain triallelic Cnga3+/- Cngb3R403Q/R403Q mutants. As in human subjects, there was a striking genotype-phenotype correlation, since the presence of 1 Cnga3-null allele exacerbated the cone dystrophy phenotype in Cngb3R403Q/R403Q mice. These findings strongly suggest a digenic and triallelic inheritance pattern in a subset of patients with achromatopsia/severe cone dystrophy linked to the CNGB3/p.R403Q mutation, with important implications for diagnosis, prognosis, and genetic counseling.
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