Dataset Information

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

ABSTRACT:

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.

SUBMITTER: Smirnov VM

PROVIDER: S-EPMC9055553 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

Smirnov Vasily M VM Nassisi Marco M Mohand-Saïd Saddek S Bonnet Crystel C Aubois Anne A Devisme Céline C Dib Thilissa T Zeitz Christina C Loundon Natalie N Marlin Sandrine S Petit Christine C Bodaghi Bahram B Sahel José-Alain JA Audo Isabelle I

Investigative ophthalmology & visual science 20220401 4

<h4>Purpose</h4>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.<h4>Methods</h4>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, ...[more]

PMID: 35481838

Similar Datasets

Project description:ImportanceBiallelic variants in CLN3 lead to a spectrum of diseases, ranging from severe neurodegeneration with retinal involvement (juvenile neuronal ceroid lipofuscinosis) to retina-restricted conditions.ObjectiveTo provide a detailed description of the retinal phenotype of patients with isolated retinal degeneration harboring biallelic CLN3 pathogenic variants and to attempt a phenotype-genotype correlation associated with this gene defect.Design, setting, and participantsThis retrospective cohort study included patients carrying biallelic CLN3 variants extracted from a cohort of patients with inherited retinal disorders (IRDs) investigated at the National Reference Center for Rare Ocular Diseases of the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts from December 2007 to August 2020. Data were analyzed from October 2019 to August 2020.Main outcome and measuresFunctional (best-corrected visual acuity, visual field, color vision, and full-field electroretinogram), morphological (multimodal retinal imaging), and clinical data from patients were collected and analyzed. Gene defect was identified by either next-generation sequencing or whole-exome sequencing and confirmed by Sanger sequencing, quantitative polymerase chain reaction, and cosegregation analysis.ResultsOf 1533 included patients, 843 (55.0%) were women and 690 (45.0%) were men. A total of 15 cases from 11 unrelated families harboring biallelic CLN3 variants were identified. All patients presented with nonsyndromic IRD. Two distinct patterns of retinal disease could be identified: a mild rod-cone degeneration of middle-age onset (n = 6; legal blindness threshold reached by 70s) and a severe retinal degeneration with early macular atrophic changes (n = 9; legal blindness threshold reached by 40s). Eleven distinct pathogenic variants were detected, of which 4 were novel. All but 1, p.(Arg405Trp), CLN3 point variants and their genotypic associations were clearly distinct between juvenile neuronal ceroid lipofuscinosis and retina-restricted disease. Mild and severe forms of retina-restricted CLN3-linked IRDs also had different genetic background.Conclusions and relevanceThese findings suggest CLN3 should be included in next-generation sequencing panels when investigating patients with nonsyndromic rod-cone dystrophy. These results document phenotype-genotype correlations associated with specific variants in CLN3. However, caution seems warranted regarding the potential neurological outcome if a pathogenic variant in CLN3 is detected in a case of presumed isolated IRD for the onset of neurological symptoms could be delayed.

Dataset Information

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

Purpose

Methods

Results

Conclusions

Publications

Retinal Phenotype of Patients with CLRN1-Associated Usher 3A Syndrome in French Light4Deaf Cohort.

Similar Datasets

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