Absent cone function and stable ophthalmic features in a non-syndromic woman with pathogenic variants in <i>CEP290</i>

CEP290-associated retinal diseases span a broad phenotypic spectrum, from Leber congenital amaurosis to milder retinal dystrophies to syndromic ciliopathies. Herein, we describe a non-syndromic 18-year-old woman with compound heterozygous pathogenic variants in CEP290 whose ophthalmic features are infantile-onset nystagmus, benign and stable fundus appearance, and lack of cone-mediated visual and retinal function. Serial examinations from infancy onward document stable achromatopsia-like ophthalmic features. No cone-mediated vision or retinal function was demonstrated. By optical coherence tomography, foveal architecture was preserved and central retinal thickness was stable for more than a decade (median 246 µm, range 232–257 µm). Testing for common CNGA3 and CNGB3 variants in early childhood was negative, as was further testing via an eight-gene achromatopsia panel. Trio exome sequencing identified compound heterozygous pathogenic CEP290 variants in trans: c.4723A>T (p.Lys1575Ter) and c.6277del (p.Val2093SerfsTer4). Notably, c.4723A>T is a nonsense variant previously shown to undergo nonsense-associated exon skipping, consistent with a hypomorphic effect that has been associated with milder CEP290-related retinal disease. These findings suggest a selective impairment of cone-mediated function with relative preservation of rod function.