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CRB1-associated retinal dystrophies in a Belgian cohort: genetic characteristics and long-term clinical follow-up
  1. Mays Talib1,
  2. Caroline Van Cauwenbergh2,3,
  3. Julie De Zaeytijd2,
  4. David Van Wynsberghe4,
  5. Elfride De Baere3,
  6. Camiel J F Boon1,5,
  7. Bart Peter Leroy2,3,6,7
  1. 1Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
  3. 3Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium
  4. 4Department of Ophthalmology, Maria Middelares General Hospital, Ghent, Belgium
  5. 5Department of Ophthalmology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
  6. 6Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
  7. 7Centre for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
  1. Correspondence to Mays Talib, Ophthalmology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands; m.talib{at}lumc.nl

Abstract

Aim To investigate the natural history in a Belgian cohort of CRB1-associated retinal dystrophies.

Methods An in-depth retrospective study focusing on visual function and retinal structure.

Results Forty patients from 35 families were included (ages: 2.5–80.1 years). In patients with a follow-up of >1 year (63%), the mean follow-up time was 12.0 years (range: 2.3–29.2 years). Based on the patient history, symptoms and/or electroretinography, 22 patients (55%) were diagnosed with retinitis pigmentosa (RP), 15 (38%) with Leber congenital amaurosis (LCA) and 3 (8%) with macular dystrophy (MD), the latter being associated with the p.(Ile167_Gly169del) mutation (in compound heterozygosity). MD later developed into a rod-cone dystrophy in one patient. Blindness at initial presentation was seen in the first decade of life in LCA, and in the fifth decade of life in RP. Eventually, 28 patients (70%) reached visual acuity-based blindness (<0.05). Visual field-based blindness (<10°) was documented in 17/25 patients (68%). Five patients (13%) developed Coats-like exudative vasculopathy. Intermediate/posterior uveitis was found in three patients (8%). Cystoid maculopathy was common in RP (9/21; 43%) and MD (3/3; 100%). Macular involvement, varying from retinal pigment epithelium alterations to complete outer retinal atrophy, was observed in all patients.

Conclusion Bi-allelic CRB1 mutations result in a range of progressive retinal disorders, most of which are generalised, with characteristically early macular involvement. Visual function and retinal structure analysis indicates a window for potential intervention with gene therapy before the fourth decade of life in RP and the first decade in LCA.

  • dystrophy
  • genetics
  • retina

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Footnotes

  • Contributors All authors have contributed substantially to this publication, as per the ICMJE criteria.

  • Funding This study was in part funded by the Curing Retinal Blindness Foundation (CJFB), and the Research Foundation Flanders (Belgium) (FWO); support: FWO Flanders Grant OZP 3G004306 (BPL).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ghent University Hospital's local ethics committee. Approval number/ID is 2018/0235 for project BC2523-TVE.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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