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Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the C1QTNF5 gene.

  • De Zaeytijd, Julie1
  • Coppieters, Frauke2, 3
  • De Bruyne, Marieke2, 3
  • Van Royen, Jasper2
  • Roels, Dimitri1
  • Six, Rani2
  • Van Cauwenbergh, Caroline1, 2, 4
  • De Baere, Elfride2, 3
  • Leroy, Bart P1, 2, 4, 5, 6
  • 1 Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium. , (Belgium)
  • 2 Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium. , (Belgium)
  • 3 Department of Biomolecular Medicine, Ghent University, Ghent, Belgium. , (Belgium)
  • 4 Department of Head & Skin, Ghent University, Ghent, Belgium. , (Belgium)
  • 5 Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • 6 Center for Cellular & Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Published Article
Ophthalmic genetics
Publication Date
Oct 01, 2021
DOI: 10.1080/13816810.2021.1923041
PMID: 33949280


Background: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy related to C1QTNF5 gene variants.Materials and methods: Twenty-six patients (21-81 years) with L-ORD due to c.562C>A p.(Pro188Thr) with a mean follow-up time of 8 years (range 1-37 years) underwent an extensive ophthalmic work-up.Results: Best-corrected visual acuity (BCVA) and visual fields were maintained up to 50 to 55 years (n = 8), with a gradual decline, but conservation of functional central vision between 55 to 65 years (n = 15), followed by a steep decrease in overall visual function beyond 65 years (n = 9). Classic anterior segment findings in L-ORD of abnormally long, anteriorly inserted lens zonules were absent in most patients (n = 24/26). In contrast, findings of iris transillumination and sphincter pupillae atrophy with poor dilation were novel. Patients presented with three completely different initial fundus phenotypes: adjoining pavingstone-like atrophic patches (type 1) (n = 6/20); tiny yellow-white subretinal dots (type 2) (n = 8/20); or larger yellow, thick, round sub-RPE drusenoid deposits (type 3) (n = 4/20). Two patients had a mixed phenotype. Although different in presentation phenotype, patients eventually all progressed to a common panretinal atrophy with diffuse intraretinal pigment migration beyond the age of 65. Progression pace, and thus visual prognosis, differed depending on presentation phenotype. Specifically, type 2 appears to have a more benign course.Conclusions: Phenotypic analysis showed three distinct presenting phenotypes with a considerable intrafamilial variability both in age of onset of clinical signs and in disease progression, with a fair visual potential (>20/40) until the seventh decade.Abbreviations: L-ORD: Late-onset retinal degeneration; C1QTNF5: complement 1Q tumor necrosis factor 5; OCT: Ocular coherence tomography; BCVA: Best-corrected visual acuity; RPE: Retinal pigment epithelium; ffERG: Full-field electroretinography; IRD: Inherited retinal dystrophy; CNV: Choroidal neovascularization; LAZ: Long anteriorly inserted zonules; AMPK: AMP-activated protein kinase; IOP: Intraocular pressure; cSLO: confocal scanning laser ophthalmoscopy; BAF: Blue light autofluorescence; NIR-AF: Near-infrared autofluorescence; NIR-R: Near-infrared reflectance; RF: Red-free; SD-OCT: Spectral domain ocular coherence tomography; HRR: Hardy-Rand-Rittler pseudo-isochromatic plates; AS: anterior segment; UBM: ultrasound biomicroscopy; PCR: Polymerase chain reaction; SNP: Single nucleotide polymorphism; VEGF: Vascular endothelial growth factor; IZ: Interdigitation zone; EZ: Ellipsoid zone; ELM: External limiting membrane; LP: Light perception; AMD: Age-related macular degeneration; SFD: Sorsby fundus dystrophy.

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