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, consecu-tive, single-center case series was performed on patients with molecularly confirmed HK1-associ-ated disease. Patients between 2016 and 2024 were included. Results: Sixty eyes from 30 patients were assessed. Thirty patients of 22 unrelated families were in-cluded. 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 au-tosomal 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 genotype-phenotype relationship and explore therapeutic options.