A Homozygous Frameshift Mutation In LRAT Causes Retinitis Punctata Albescens

Abstract

Purpose: : To determine the genetic defect and to describe the clinical characteristics in patients with retinitis punctata albescens (RPA) and fundus albipunctatus (FAP).

Methods: : Thirteen patients were collected from eight families with a retinal dystrophy characterized by tiny yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmological examinations, including visual field assessment, fundus photography, and electroretinography. Optical coherence tomography (OCT) and fundus autofluorescence were performed in three patients. DNA samples of all patients were screened for mutations in RLBP1, and for mutations in RDH5 in patients who did not carry mutations in RLBP1. DNA samples of two sibling-pairs of nonconsanguineous families who carried mutations neither in RLBP1 nor in RDH5 were analyzed by genome-wide homozygosity mapping. Sequence analysis was performed of LRAT; a candidate gene in a shared homozygous region.

Results: : Electroretinography led to the diagnosis of FAP in one patient, FAP with cone dystrophy in one patient and RPA in the other patients. OCT imaging revealed no differences in localization and shape of the white dots in FAP and RPA patients. A homozygous frameshift mutation was identified in LRAT infour patients with RPA. Also, mutations in RLBP1 were identified in six patients with RPA and one patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 andsuffered from FAP with mild maculopathy.

Conclusions: : A genetic defect was identified in LRAT as a novel cause of RPA. LRAT is therefore the fourth gene involved in the visual cycle that may cause a white-dot retinopathy. We also revealed that mutations in RLBP1 may lead to FAP with cone dystrophy.

Keywords: retinal degenerations: hereditary • genetics