Autosomal dominant pigmented paravenous retinochoroidal atrophy associated with pathogenic variant in HK1 gene.

PURPOSE: To determine the clinical characteristics and the causative genetic variant of a familial case of pigmented paravenous retinochoroidal atrophy (PPRCA).

METHODS

Whole exome sequencing (WES) was performed on ten individuals from four families. Their clinical characteristics were determined and compared to other patients with other inherited retinal dystrophies (IRDs) who had HK1 gene variants.

RESULTS

A known heterozygous pathogenic variant in the hexokinase 1 (HK1) gene, c.2539G > A; p.Glu847Lys, segregated with the six family members. Four affected family members had signs of PPRCA associated with mild macular degeneration detected by fundus autofluorescence and optical coherence tomography. In addition, four patients from three families with the same variant were diagnosed with cone-rod dystrophy, retinitis pigmentosa, and enhanced S-cone syndrome. They had different degrees of macular and mid-peripheral degeneration but lacked the pathogenic features of PPRCA.

CONCLUSION

This is the first study of familial PPRCA associated with the pathogenic HK1 variant. Patients with the HK1 variant had different clinical diagnoses based on the variations in the phenotypic severities. Their visual acuity and electroretinograms were less severely altered than expected given the structural abnormalities observed around the macula in imaging analyses.