A novel pathogenic CRB1 variant presenting as Leber Congenital Amaurosis 8 and evaluation of gene editing feasibility.

Autor: Sylla MM; Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.; Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA.; State University of New York at Downstate Health Sciences University, Brooklyn, NY, USA., Kolesinkova M; Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.; Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA.; State University of New York at Downstate Health Sciences University, Brooklyn, NY, USA., da Costa BL; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Maumenee IH; Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.; Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA., Tsang SH; Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA.; Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Department of Ophthalmology, Columbia University, New York, NY, USA.; Department of Biomedical Engineering, Columbia University, New York, NY, USA.; Columbia Stem Cell Initiative, Columbia University, New York, NY, USA.; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA., Quinn PMJ; Department of Ophthalmology, Columbia University Irving Medical Center, New York, NY, USA. pq2138@cumc.columbia.edu.; Department of Ophthalmology, Columbia University Irving Medical Center, Hammer Health Sciences Building, 701 West 168th Street, New York, NY, 10032, USA. pq2138@cumc.columbia.edu.
Jazyk: angličtina
Zdroj: Documenta ophthalmologica. Advances in ophthalmology [Doc Ophthalmol] 2023 Dec; Vol. 147 (3), pp. 217-224. Date of Electronic Publication: 2023 Oct 07.
DOI: 10.1007/s10633-023-09951-w
Abstrakt: Introduction: Leber Congenital Amaurosis (LCA) is an inherited retinal disease that presents in infancy with severely decreased vision, nystagmus, and extinguished electroretinography findings. LCA8 is linked to variants in the Crumbs homolog 1 (CRB1) gene.
Case Description: We report a novel CRB1 variant in a 14-year-old male presenting with nystagmus, worsening vision, and inability to fixate on toys in his infancy. Color fundus photography revealed nummular pigments in the macula and periphery. Imaging studies revealed thickened retina on standard domain optical coherence tomography and widespread atrophy of the retinal pigment epithelium on autofluorescence. Full-field electroretinography revealed extinguished scotopic and significantly reduced photopic responses. Genetic testing demonstrated a novel homozygous variant, c.3057 T > A; p.(Tyr1019Ter), in the CRB1 gene. This variant is not currently amenable to base editing, however, in silico analysis revealed several potential prime editing strategies for correction.
Conclusion: This case presentation is consistent with LCA8, suggesting pathogenicity of this novel variant and expanding our knowledge of disease-causing CRB1 variants.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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