A novel PIKFYVE mutation in fleck corneal dystrophy

Area of Science:

• Ophthalmology and Genetics
• Corneal Dystrophies
• Molecular Diagnostics

Background:

• Fleck corneal dystrophy (CFD) is a rare inherited eye condition affecting corneal clarity.
• Understanding the genetic underpinnings of CFD is crucial for diagnosis and potential therapeutic strategies.
• Previous research has identified various genetic mutations associated with different forms of corneal dystrophies.

Purpose of the Study:

• To conduct a clinical and molecular evaluation of fleck corneal dystrophy (CFD) within a Greek family.
• To identify the specific genetic mutation responsible for CFD in this multi-generational family.
• To analyze the inheritance pattern and clinical presentation of CFD across five generations.

Main Methods:

• Clinical examination of twenty family members across five generations using slit-lamp biomicroscopy.
• Molecular analysis of the phosphoinositide kinase, five finger-containing (PIKFYVE) gene in affected and unaffected individuals.
• Utilized direct sequencing and denaturing high-performance liquid chromatography (DHPLC) for genetic mutation screening.

Main Results:

• Six family members were clinically diagnosed with fleck corneal dystrophy (CFD).
• A novel mutation, c.3060-3063delCCTT (p.P968Vfs23), was identified in the PIKFYVE gene in all affected individuals.
• This PIKFYVE mutation segregated with the disease and was absent in unaffected family members; early cataract formation was noted in two patients.

Conclusions:

• The novel c.3060-3063delCCTT (p.P968Vfs23) mutation in the PIKFYVE gene is the causative genetic defect for fleck corneal dystrophy in this Greek family.
• This study highlights the importance of molecular genetic analysis in diagnosing inherited corneal diseases.
• The findings contribute to the genetic landscape of corneal dystrophies and provide a basis for future research.