Usher Syndrome Type 2D Associated With a Novel Homozygous Whrn c.74dup Variant: A Case Report

Variants of the WHRN/DFNB31 gene cause Usher syndrome type 2D (USH2D), a rare subtype of Usher syndrome. Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive retinal degeneration due to retinitis pigmentosa. We report the case of a 63-year-old woman with clinical and genetic findings consistent with USH2D. Ophthalmic evaluation demonstrated reduced visual acuity, bilateral optic disc pallor, mid-peripheral bony spicules, vascular attenuation, and macular abnormalities. Full-field electroretinography showed non-recordable photopic and scotopic responses bilaterally, consistent with extinguished rod and cone responses. Macular optical coherence tomography demonstrated a central subfield thickness of 220 µm (oculus dexter or right eye (OD)) and 235 µm (oculus sinister or left eye (OS)), a cube volume of 7.8 mm³ OD and 6.5 mm³ OS, and an average cube thickness of 215 µm OD and 180 µm OS, supporting structural macular involvement. Electrooculography demonstrated an abnormal Arden ratio of 1.58 in both eyes, consistent with retinal pigment epithelium dysfunction. Based on these ocular findings, the patient was diagnosed with retinitis pigmentosa. Genetic testing with next-generation sequencing identified a homozygous pathogenic WHRN c.74dup (p.Gly26Argfs*153) variant. To our knowledge, this specific frameshift variant has not been previously reported in the literature in affected individuals with WHRN-related disease. This case highlights the importance of genetic testing and multimodal ophthalmic evaluation in patients with inherited retinal dystrophies and contributes to the limited literature describing Usher syndrome due to WHRN mutations.