Phenotype variations of retinal dystrophies caused by mutations in the RLBP1 gene

Acta Ophthalmol. 2015 Jun;93(4):e281-6. doi: 10.1111/aos.12573. Epub 2014 Nov 27.

Abstract

Purpose: Mutations in the RLBP1 gene encoding the cellular retinaldehyde-binding protein (CRALBP) cause autosomal recessive progressive retinopathy, such as retinitis punctata albescens (RPA), Bothnia-type dystrophy (BD), Newfoundland rod-cone dystrophy (NFRCD), retinitis pigmentosa (RP) and fundus albipunctatus (FA). We present the clinical heterogeneity and genetic findings of seven patients from five families with RLBP1 mutations, including three novel mutations.

Methods: Seven patients underwent complete ophthalmological examination including psychophysical tests (visual acuity, colour vision, visual field, dark adaptation) and electrophysiology (Ganzfeld and multifocal ERG). Additionally, fundus photography, autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) recordings were performed. Genomic DNA was analysed by high-throughput sequencing for all RP-related genes in a diagnostic set-up.

Results: The patients presented with variable phenotypes, including RPA, BD, RP and a mild form of NFRCD. No detectable or severely depressed responses in electrophysiological examinations were seen in all cases. Visual field constriction was variable among individuals. Severely reduced visual acuity was only observed in the patient presenting with BD. The other patients retained mild to moderate reduction of visual function. Despite the morphological differences, central retinal thinning - as a common feature - could be observed.

Conclusions: The fact that different mutations in RLBP1 are correlated with quite different morphological and functional characteristics outlines the complexity of the protein. Identifying new mutations and comparing the different phenotypes may help to better understand the function of the protein and the consequences in pathological changes that involve RPE and choroid.

Keywords: RLBP1 mutations; genotype-phenotype correlations; retinitis pigmentosa; retinitis punctata albescens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carrier Proteins / genetics*
  • Child
  • Electroretinography
  • Female
  • Fluorescein Angiography
  • Genetic Association Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics*
  • Siblings
  • Tomography, Optical Coherence
  • Visual Acuity / physiology
  • Young Adult

Substances

  • 11-cis-retinal-binding protein
  • Carrier Proteins