INTRAFAMILIAL VARIABILITY OF IMPG1 -ASSOCIATED VITELLIFORM DYSTROPHY

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Vitelliform macular dystrophies are inherited retinal disorders characterized by yellow, yolk-like deposits in the macula.
• Mutations in the IMPG1 gene have been previously linked to vitelliform macular dystrophy phenotypes.
• Understanding the genetic basis and clinical variability is crucial for diagnosis and management.

Purpose of the Study:

• To investigate the clinical and multimodal imaging findings in two siblings with distinct vitelliform phenotypes.
• To identify the genetic cause, specifically focusing on a novel deletion in the IMPG1 gene.

Main Methods:

• A case series of two siblings presenting with vitelliform lesions.
• Multimodal imaging including optical coherence tomography (OCT), fundus color, short-wavelength fundus autofluorescence (SW-FAF), and fluorescein angiography.
• Genetic testing for inherited retinal disorders, including analysis of the IMPG1 gene.

Main Results:

• Both siblings presented with bilateral vitelliform lesions, but with different topographical distributions.
• The brother had single foveal lesions, while his sister had asymptomatic multifocal extrafoveal lesions.
• Identical heterozygous deletion in exon 7 of the IMPG1 gene was identified in both siblings.

Conclusions:

• A novel IMPG1 gene deletion in exon 7 is associated with vitelliform macular dystrophy.
• The findings support the pathogenicity of IMPG1 variants in causing this condition.
• Intrafamilial variability in lesion presentation suggests genetic modifiers influence disease expression.