Non-syndromic retinitis pigmentosa with bilateral retinal neovascularization due to HGSNAT mutation.

Abstract

To describe a case of non-syndromic retinitis pigmentosa (RP) caused by presumed compound heterozygous A615T and T522M mutations in HGSNAT, characterized by bilateral cystoid macular edema (CME) and retinal neovascularization (NV). Case report. The patient underwent clinical evaluation, multimodal imaging and Next Generation panel sequencing. In silico analysis was performed with PolyPhen-2, SIFT and Mutation Taster. Segregation analysis was not available. A 35 year-old hypertensive man presented with nyctalopia, photopsia, and difficulty reading for six months. He had no family history of visual deficits. Best-corrected visual acuity (BCVA) was 20/25 in the right eye (OD) and 20/20 in the left eye (OS). Examination revealed mid-peripheral bone spicules and macular NV in both eyes (OU). Multimodal imaging demonstrated CME, ellipsoid band loss outside the central macula, and leakage from the NV in both eyes. Sequencing detected four mutations in three genes, including two heterozygous mutations in HGSNAT (c.1843G>A, p.A615T and c.1565C>T, p.T522M). A615T is a pathogenic, hypomorphic mutation. T522M has not been previously phenotypically described. It is predicted damaging by in silico analysis and occurs at a conserved position near the eighth transmembrane domain, adjacent to residues in which missense mutations result in protein misfolding. This is, to our knowledge, the first reported case of retinal NV in a case of non-syndromic RP due to HGSNAT mutation. The T522M variant likely functions as a severe mutation alongside the hypomorphic A615T mutation. These findings expand the genotypic and phenotypic spectrum of non-syndromic RP.