Purpose: Biallelic variants in CLRN1 are responsible for Usher syndrome 3A and non-syndromic rod-cone dystrophy (RCD). Retinal findings in Usher syndrome 3A have not been well defined. We report the detailed phenotypic description of RCD associated with CLRN1 variants in a prospective cohort.
Methods: Patients were clinically investigated at the National Reference Center for rare ocular diseases at the Quinze-Vingts Hospital, Paris, France. Best-corrected visual acuity (BCVA) tests, Goldmann perimetry, full-field electroretinography (ffERG), retinal photography, near-infrared reflectance, short-wavelength and near-infrared autofluorescence, and optical coherence tomography (OCT) were performed for all patients.
Results: Four patients from four unrelated families were recruited. Mean follow-up was 11 years for three patients, and only baseline data were available for one subject. Median BCVA at baseline was 0.2 logMAR (range, 0.3-0). ffERG responses were undetectable in all subjects. The III4e isopter of the Goldmann visual field was constricted to 10°. The retinal phenotype was consistent in all patients: small whitish granular atrophic areas were organized in a network pattern around the macula and in the midperiphery. OCT showed intraretinal microcysts in all patients. Upon follow-up, all patients experienced a progressive BCVA loss and further visual field constriction. Four distinct pathogenic variants were identified in our patients: two missense (c.144T>G, p.(Asn48Lys) and c.368C>A, p.(Ala123Asp)) and two frameshift variants (c.176del, p.(Gly59Valfs*13) and c.230dup, p.(Ala78Serfs*52)).
Conclusions: RCD in Usher 3A syndrome has some distinctive features. It is a severe photoreceptor dystrophy with whitish granular posterior pole appearance and cystic maculopathy.
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http://dx.doi.org/10.1167/iovs.63.4.25 | DOI Listing |
Orphanet J Rare Dis
January 2025
Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Hospitais da Universidade de Coimbra (HUC), ULS Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal.
Background: Syndromic genetic disorders affecting vision can also cause hearing loss, and Usher syndrome is by far the most common etiology. However, many other conditions can present dual sensory impairment. Accurate diagnosis is essential for providing patients with genetic counseling, prognostic information, and appropriate resources.
View Article and Find Full Text PDFJ Sleep Res
December 2024
Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands.
This study aimed to improve our understanding of sleep problems as a comorbidity of hereditary deaf-blindness due to Usher syndrome type 2a. Fifteen patients with Usher syndrome type 2a with a conclusive genetic diagnosis and 15 unaffected controls participated in comprehensive sleep and activity assessments for 2 weeks, using the MotionWatch 8 actigraph and consensus sleep diary. Various sleep parameters including sleep opportunity window, sleep latency, sleep efficiency, and self-reported sleep quality were analysed.
View Article and Find Full Text PDFProg Retin Eye Res
December 2024
Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20-30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives.
View Article and Find Full Text PDFEur J Hum Genet
December 2024
Molecular, Cellular, and Genomic Biomedicine Group, IIS-La Fe, Valencia, Spain.
The AGBL5 gene encodes for the Cytoplasmic Carboxypeptidase 5 (CCP5), an α-tubulin deglutamylase that cleaves the γ-carboxyl-linked branching point of glutamylated tubulin. To date, pathogenic variants in AGBL5 have been associated only with isolated retinitis pigmentosa (RP). Hearing loss has not been reported in AGBL5-caused retinal disease.
View Article and Find Full Text PDFDev Med Child Neurol
December 2024
Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh, Edinburgh, UK.
Aim: To extend the findings of a previous clinical trial suggesting combined abacavir (ABC), lamivudine (3TC), and zidovudine (AZT) reduces type I interferon (IFN) signalling in Aicardi-Goutières syndrome (AGS).
Method: This was an open label, non-placebo-controlled phase II clinical trial (NCT04731103) in patients less than 16 years with any of five AGS genotypes. The effect of ABC or 3TC individually, or of combined ABC + 3TC + AZT, on IFN-stimulated gene (ISG) expression (primary outcome) and IFN-alpha protein (secondary outcome) in blood was assessed.
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