Variants of Uncertain Significance: Twins With Identical Pathogenic Gene Mutations in Retinitis Punctata Albescens

Area of Science:

• Ophthalmology
• Genetics
• Medical Research

Background:

• Retinitis punctata albescens (RPA) is an inherited retinal degenerative disease characterized by specific fundus findings.
• Understanding the genetic basis and phenotypic variability of RPA is crucial for accurate diagnosis and classification.

Observation:

• Identical twin sisters exhibited highly similar clinical symptoms, fundus examinations, and ophthalmic test results consistent with RPA.
• Key features included pathognomonic white retinal flecks, extensive midperipheral retinal pigment epithelium atrophy, and pigmentary changes.

Findings:

• Genetic testing identified two mutations in the RLBP1 gene in both sisters.
• One mutation was pathogenic for RPA, while the other was a variant of uncertain significance previously linked to RPA.

Implications:

• This case highlights the utility of studying identical twins to understand genetic mutations and phenotypic expression in inherited retinal diseases.
• The findings contribute to the ongoing classification of pathogenic mutations associated with retinitis punctata albescens.