Biallelic mutations in RBP3 encoding interphotoreceptor binding protein (IRBP) cause an early onset retinal dystrophy and high myopia

Abstract

Purpose: To present a detailed clinical and molecular study of four patients from two consanguineous families with a similar childhood-onset retinal dystrophy resulting from novel biallelic nonsense mutations in RBP3.

Methods: Four children with mutations in RBP3 encoding interphotoreceptor binding protein (IRBP) were ascertained by whole exome sequencing and subsequent direct Sanger sequencing. Detailed phenotyping was performed including full clinical evaluation, pattern and full-field electroretinography (PERG; ERG), fundus photography, fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (OCT).

Results: Two novel biallelic nonsense mutations (c.1530T>A ; p.Y510* and c.3454G>T ; p.E1152*) in RBP3 were identified in four patients from two families. All four patients had a similar, unusual retinal dystrophy characterised by childhood-onset high myopia and an unremarkable fundus appearance. The ERGs showed generalised rod and cone dysfunction in all cases, with greater rod involvement in three. PERG P50 ranged normal to undetectable, indicating variable macular involvement. FAF imaging showed multiple paracentral foci of low density in one patient and patchy increased FAF in the region of the vascular arcades in another. The OCT showed loss of outer retinal bands over eccentric macular areas in all 4 cases.

Conclusions: This report is the first to describe the retinal dystrophy in children caused by biallelic RBP3 mutations. The retinal phenotype is characterised by early onset, normal fundi other than high myopia, and generalized retinal dysfunction with variable macular involvement. Mutations in RBP3 should be considered in children with high myopia and retinal dystrophy, particularly when there are minimal fundus changes.<br /> <br />