Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• The ABCA4 gene is associated with retinal diseases like Stargardt disease.
• The GPR143 gene is linked to X-linked ocular albinism (OA1).
• Complex genetic interactions can lead to overlapping ocular phenotypes.

Purpose of the Study:

• To characterize the phenotype in a family with mutations in both ABCA4 and GPR143 genes.
• To investigate the combined effects of pathogenic mutations in these two genes on retinal structure and function.

Main Methods:

• Clinical evaluation of a two-generation family.
• Quantitative autofluorescence imaging (qAF), spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography (ERG).
• Complete sequencing of ABCA4 and GPR143 genes.

Main Results:

• Affected individuals showed bull's eye lesions, elevated qAF, and mild cone dysfunction on ERG.
• ABCA4 mutations (p.L541P, p.G1961E) and a novel GPR143 variant (p.Y157C) were identified.
• The father with the GPR143 variant showed only abnormal macular NIR-AF, suggesting variable expressivity.

Conclusions:

• Co-inheritance of ABCA4 and GPR143 mutations can result in a complex phenotype overlapping Stargardt disease and OA1.
• The father's presentation indicates potential mild expressivity or reduced penetrance of OA1.
• This study highlights the importance of comprehensive genetic analysis in families with complex retinal disorders.