A homozygous frameshift mutation in LRAT causes retinitis punctata albescens

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

DESIGN: Case series/observational study.

PARTICIPANTS: We included 13 patients affected by RPA or FAP.

METHODS: Thirteen patients were collected from 8 families with a retinal dystrophy characterized by tiny, yellow-white dots on funduscopy, typical for FAP or RPA. All patients underwent full ophthalmologic examinations, including visual field assessment. Fundus photography, and electroretinography were performed in 12 patients, and optical coherence tomography and fundus autofluorescence were performed in 4 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 2 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.

MAIN OUTCOME MEASURES: We assessed DNA sequence variants, best-corrected visual acuity, fundus appearance, visual field measurements, electroretinogram responses, optical coherence tomography, and fundus autofluorescence.

RESULTS: A homozygous frameshift mutation was identified in LRAT in 4 patients with RPA. Mutations in RLBP1 were identified in 7 patients with RPA and in 1 patient with FAP and cone dystrophy. One patient had compound heterozygous mutations in RDH5 and suffered 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.