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Yousef J Cruz Inigo, Kendra Klein, Benjamin Bakall; Phenotype-Genotype Correlation among Patients with Pathogenic CRB1 gene Variants. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2333. doi: https://doi.org/.
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To report the genotype-phenotype correlation among patients with pathogenic CRB1 gene variants from a single retina subspecialty practice in Arizona.
We reviewed the medical records and molecular testing results from all retinal dystrophy patients with two CRB1 gene variants, evaluated in a single retina subspecialty practice in Arizona. The HGMD database was consulted and Poly-Phen2, SIFT, Mutation Taster and Alamut Visual V2.9.0 pathogenicity prediction software were utilized to evaluate the variants. Patients were diagnosed based on a combination of ophthalmic exam, retinal imaging and electroretinogram (ERG).
Eight patients with CRB1 gene variants were selected including seven patients with Leber congenital amaurosis (LCA) and one patient with retinitis pigmentosa (RP). All variants were classified as likely pathogenic according to the criteria of effect in the protein structure, amino acid conservation, frequency in the population and classification by pathogenic predictors. Three novel CRB1 gene variants were identified: two missense variants in four patients with LCA (p.Phe946Cys, and p.Asn880Ser) and a frameshift variant in one patient with RP (p.Ile961Tyrfs*27). Patients with LCA had decreased central vision, nystagmus and generalized retinal dystrophy with para-arteriolar preservation of the retinal pigment epithelium. Clinical findings for the RP patient included progressive visual field constriction and pigmentary retinal dystrophy with preserved central vision in the first 3 decades of life. All tested patients had reduced scotopic and photopic ERG responses.
Our study has identified three novel pathogenic CRB1 gene variants for patients with LCA and RP. This study adds to our current knowledge about disease-causing variants in the CRB1 gene that may contribute to future therapy.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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