Nonsyndromic Retinitis Pigmentosa With Pathogenic CEP290 Mutations.

Abstract

CEP290 variants, commonly associated with Leber congenital amaurosis, cause severe visual impairment within the first year of life. Herein, we report a unique case of nonsyndromic retinitis pigmentosa with foveal sparing and preserved central vision in a patient harboring two pathogenic CEP290 variants. A 28-year-old woman presented with long-standing poor peripheral vision and nyctalopia since childhood, but with visual acuity of 20/25 bilaterally. Examination showed retinal arteriolar attenuation, diffuse foveal-sparing retinal atrophy, and peripheral bone spicule pigmentation. Genetic testing identified two pathogenic nonsense mutations in CEP290 (c.1666del and c.4057G>T) and heterozygous missense mutations in BBS5 (c.715A>G), PDE6A (c.367G>T), and RPGR (c.2594_2596del), which were variants of unknown significance. Although nonsense mutations in CEP290 are associated with severe and early-onset vision loss, our patient demonstrated a mild retinitis pigmentosa phenotype with stable disease over 6 months. This case expands the phenotypic spectrum of CEP290-associated diseases and suggests a potential role for genetic modifiers in disease severity. [Ophthalmic Surg Lasers Imaging Retina 2025;56:XX-XX.].