Genotypic and Phenotypic Characterization of Hexokinase 1 p.Glu847Lys Variant Causing Autosomal Dominant Pericentral Retinitis Pigmentosa.

Background and objective: The aim of this study was to clinically and molecularly characterize the largest cohort of patients with HK1 associated retinal disease. Hexokinase 1 (HK1) variants have been reported to cause retinitis pigmentosa (RP), but a clearly defined genotype-phenotype correlation has not been well established.

Patients and methods: A retrospective, consecutive, single-center case series was performed on patients with molecularly confirmed HK1-associated disease. Patients between 2016 and 2024 were included.

Results: Sixty eyes from 30 patients were assessed. Thirty patients of 22 unrelated families were included. The median age at presentation was 53.5 years old, and the median age of disease symptom onset was 36 years old. The p.Glu847Lys variant was exhibited by 97% of the patients. Median best-recorded visual acuity was 20/28. Pericentral RP was the predominant phenotype (90% of patients).

Conclusion: HK1 p.Glu847Lys variant was found to be associated with a less severe phenotype of autosomal dominant retinitis pigmentosa (adRP) as compared to other forms of adRP based on clinical presentation and electrophysiology. Future studies are necessary to better understand the genotypephenotype relationship and explore therapeutic options. [Ophthalmic Surg Lasers Imaging Retina 2025;56:XX-XX.].