The phenotypic variability of HK1-associated retinal dystrophy

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Inherited retinal dystrophies (IRDs) are a diverse group of genetic disorders affecting photoreceptor cells.
• A single IRD-causing genetic variant can manifest with varied clinical symptoms, indicating pleiotropic effects.
• The HK1 p.E851K variant was previously associated with autosomal dominant retinitis pigmentosa (RP).

Purpose of the Study:

• To investigate the clinical spectrum associated with the HK1 p.E851K variant in four unrelated families.
• To explore the pleiotropic potential of a known IRD-causing variant.
• To deepen the understanding of hexokinase's role in retinal disease pathogenesis.

Main Methods:

• Clinical phenotyping of four unrelated families with the HK1 p.E851K variant.
• Detailed ophthalmological examinations to document retinal symptoms.
• Genetic analysis to confirm the presence of the HK1 p.E851K variant.

Main Results:

• The HK1 p.E851K variant was identified in four IRD families.
• Beyond retinitis pigmentosa, the variant also caused dominant macular dystrophy and cone-rod dystrophy.
• These findings demonstrate that the HK1 p.E851K variant affects cone photoreceptors more prominently than rods in some cases.

Conclusions:

• The HK1 p.E851K variant exhibits significant pleiotropy, causing multiple forms of inherited retinal dystrophy.
• This study expands the known clinical manifestations of the HK1 p.E851K variant.
• Hexokinase's involvement in retinal pathogenesis is more complex than previously understood, with implications for IRD research.