ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
GUCA1A mutation causes maculopathy in a five-generation family with a wide spectrum of severity.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates.Frontiers in genetics · 2022Pooled it
- A miR-219-5p-bmal1b negative feedback loop contributes to circadian regulation in zebrafish.Communications biology · 2024Article
- Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry.International journal of molecular sciences · 2022Article
- Molecular Properties of Human Guanylate Cyclase-Activating Protein 3 (GCAP3) and Its Possible Association with Retinitis Pigmentosa.International journal of molecular sciences · 2022Article
- Retinal imaging in inherited retinal diseases.Annals of eye science · 2020Article
- The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology.Human molecular genetics · 2020Article
- Constitutive Activation of Guanylate Cyclase by the G86R GCAP1 Variant Is Due to "Locking" Cation-π Interactions that Impair the Activator-to-Inhibitor Structural Transition.International journal of molecular sciences · 2020Article
- Characterization of GUCA1A-associated dominant cone/cone-rod dystrophy: low prevalence among Japanese patients with inherited retinal dystrophies.Scientific reports · 2019Article
- Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy.The British journal of ophthalmology · 2019Review
- Functional characterization of a novelMolecular vision · 2019Article
- Distinct mutations with different inheritance mode caused similar retinal dystrophies in one family: a demonstration of the importance of genetic annotations in complicated pedigrees.Journal of translational medicine · 2018Article
- Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina.Scientific reports · 2018Article
- Article
- Molecular properties of human guanylate cyclase-activating protein 2 (GCAP2) and its retinal dystrophy-associated variant G157R.The Journal of biological chemistryArticle
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Authors and funding
15 authors at 10 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to investigate the genetic basis and pathogenic mechanism of variable maculopathies, ranging from mild photoreceptor degeneration to central areolar choroidal dystrophy, in a five-generation family.
methodsClinical characterizations, whole-exome sequencing, and genome-wide linkage analysis were carried out on the family. Zebrafish models were used to investigate the pathogenesis of GUCA1A mutations.
resultsA novel mutation, GUCA1A p.R120L, was identified in the family and predicted to alter the tertiary structure of guanylyl cyclase-activating protein 1, a photoreceptor-expressed protein encoded by the GUCA1A gene. The mutation was shown in zebrafish to cause significant disruptions in photoreceptors and retinal pigment epithelium, together with atrophies of retinal vessels and choriocapillaris. Those phenotypes could not be fully rescued by exogenous wild-type GUCA1A, suggesting a likely gain-of-function mechanism for p.R120L. GUCA1A p.D100E, another mutation previously implicated in cone dystrophy, also impaired the retinal pigment epithelium and photoreceptors in zebrafish, but probably via a dominant negative effect.
conclusionWe conclude that GUCA1A mutations could cause significant variability in maculopathies, including central areolar choroidal dystrophy, which represents a severe pattern of maculopathy. The diverse pathogenic modes of GUCA1A mutations may explain the phenotypic diversities.Genet Med advance online publication 26 January 2017.
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