A Possible Pseudociliopathy in a Patient With Retinitis Pigmentosa and Compound Heterozygous GNB3 Variants: A Case Report

Retinitis pigmentosa (RP) comprises a group of inherited retinal disorders in which photoreceptor degeneration results in progressive peripheral visual field loss and, at later stages, impairment of central vision.Biallelic guanine nucleotide-binding protein beta-3 subunit (GNB3) variants have previously been associated with autosomal recessive congenital stationary night blindness (CSNB) and childhood-onset retinopathy, with the human phenotypic spectrum described to date differing from the progressive rod-cone degeneration observed in retinitis pigmentosa.We report a 20-year-old male patient with a retinal phenotype consistent with retinitis pigmentosa (RP), compound heterozygous GNB3 variants of uncertain significance, and a reported diagnosis of Crohn's disease.Ophthalmic evaluation showed best-corrected visual acuity of 20/30+2 in both eyes, bilateral optic disc pallor, attenuation of retinal vessels, peripheral bone-spicule pigmentation, decreased macular volume, marked retinal nerve fiber layer thinning, and severe bilateral visual field loss.Next-generation sequencing (NGS) identified two heterozygous GNB3 variants of uncertain significance, c.667del (p.Thr223Leufs*39) and c.680C>T (p.Ser227Leu), located in trans, consistent with compound heterozygosity.Although GNB3 has been investigated in functional gastrointestinal disorders such as irritable bowel syndrome, available evidence does not establish an association between GNB3 variants and Crohn's disease.To our knowledge, this is the first reported case of RP in a patient with compound heterozygous GNB3 variants of uncertain significance.Because β3 subunit of the heterotrimeric G protein (Gβ3) functions in G-protein-mediated retinal signal transduction rather than the ciliary trafficking machinery, we further propose the term "pseudociliopathy" as a conceptual framework: a ciliopathy phenocopy in which disruption of intracellular signaling produces a retinal phenotype resembling those observed in true ciliopathies.This case suggests that the phenotypic spectrum of GNB3-associated retinal disease may extend beyond the stationary retinal disorders previously described and highlights the need for additional genotype-phenotype correlation studies and functional validation.