The Phenotype of Early Onset Severe Retinal Dystrophy (EOSRD) in Patients With RDH12 Mutations

Abstract

Purpose: : To describe the ocular phenotype in patients with mutations in RDH12.

Methods: : DNA samples from 220 patients with EOSRD underwent direct sequencing of all coding exons of RDH12. Patients underwent detailed ophthalmological evaluation including Goldmann perimetry, colour vision, biometric measurements, fundal photography, optical coherence tomography, retinal autofluoresence imaging and electroretinography.

Results: : RDH12 mutations were identified in 15 patients from 10 families. In 6 families affected individuals were compound heterozygotes . Nine affected individuals were homozygous for RDH12 mutations; eight novel variants were identified. These sequence changes segregated appropriately in the families and were absent from 100 control chromosomes. One patient had Leber Congenital Amaurosis with a severe visual deficit noted in the first year of life. In the other 14 patients, initial symptoms were noted between 3 and 6 years of age. Most patients reported poor night vision, reduced central vision and peripheral field loss during the first decade; the majority were low hypermetropes. All patients have an extensive peripheral pigmentary retinopathy and macular atrophy associated with yellow discoloration. Electrophysiological investigation showed severe rod and cone dysfunction at diagnosis consistent with the spectrum of EOSRD.

Conclusions: : In this study approximately 5% of patients with EOSRD had mutations in RDH12. There is early onset of night blindness with central visual loss and severe field constriction in the first decade. The distinctive retinal phenotype allows targeted molecular screening in patients with EOSRD. Photoreceptor cell death occurs early; the window for therapeutic intervention is short, within the first decade.

Keywords: retinal degenerations: hereditary • mutations • genetics