The Clinical Characteristics of Patients With Retinal Dysfunction Due to Biallelic Mutation of RDH5

Abstract

Purpose: : To determine the spectrum of retinal dysfunction in patients with RDH5 mutation.

Methods: : Patients with fundus albipunctatus were ascertained in the clinics at Moorfields Eye Hospital. Fundus photography, autofluorescence (AF) imaging and pattern and full-field electroretinography (PERG; ERG) were performed. Leukocyte genomic DNA was extracted and the coding regions and intron-exon boundaries of RLBP1 and RDH5 were sequenced.

Results: : Four patients (age range 17-42 years, 3 males) exhibiting fundus albipunctatus had a normal RLBP1 sequence. Visual acuity was normal in all cases. White spots in the posterior pole in the youngest subject correlated with diffuse foci of hyperfluorescence on AF. One 26-year-old subject had macular RPE pigment irregularity. PERGs revealed significant macular dysfunction in one 36-year-old subject. Standard ERGs showed rod-system dysfunction in all cases; there was cone system involvement in the three oldest patients. Following prolonged dark adaptation, rod-mediated ERGs normalized in three cases but in the 36-year-old with the most severe cone system dysfunction, there was only partial rod ERG recovery. 5 novel RDH5 mutations in 8 alleles of the four patients were detected (c.98T>C, p.I33T; c.712G>T, p.G238W; c.417G>T, p.G139V; c.956T>C, X319R; c.824-825del, p.R275fs).

Conclusions: : Novel mutations in RDH5 were found in 4 patients with normal visual acuity and variable fundi and phenotypes. White spots in the fundus were most prominent in younger patients and may correlate with hyperfluorescence on AF. There was normalization of the rod ERGs following extended dark adaptation in all but one patient.

Keywords: retinoids/retinoid binding proteins • genetics • electroretinography: clinical