A novel homozygous frameshift variant in the cellular retinaldehyde-binding protein 1 (RLBP1) gene causes retinitis punctata albescens

Abstract

Background Retinitis punctata albescens is a form of retinitis pigmentosa characterized by white fleck-like deposits in the fundus, in most cases caused by pathogenic variants in RLBP1 gene. The purpose of this work is to report the phenotypic and genotypic data of a patient with retinitis punctata albescens carrying a deletion in the RLBP1 gene. Results An 8-year-old Caucasian female has been complaining of nyctalopia for the last 2 years. No other ocular symptoms were present. No relevant past medical or familiar history was described. At clinical examination, the patient’s best-corrected visual acuity was 20/20 in both eyes. Anterior segment evaluation and intraocular pressure were normal in both eyes. At fundoscopy, multiple punctate whitish-yellow fleck-like lesions were observed in the proximity of temporal superior and inferior vascular arcades. Scotopic electroretinogram demonstrated severely reduced rod response, without improvement or recovery of rod system function after prolonged dark adaptation. Blood DNA samples of this patient and from her parents were screened for causal variants in RLBP1, RDH5, and PRPH2. Conclusion A probable pathogenic frameshift variant was identified in homozygosity in the RLBP1 gene with an autosomal recessive transmission as another cause of retinitis punctata albescens. This DNA variant will aid ongoing functional studies and add to our understanding of the molecular pathology about RLBP1-associated retinopathies.

Novel variants in the RDH5 Gene in a Chinese Han family with fundus albipunctatus

“…However, other two genes, retinaldehyde binding protein 1 (RLBP1) gene [ 31 , 32 ] and RPE-specific protein (RPE65) gene [ 33 ], can also lead to FA. Mutations in RLBP1 gene are also associated with RPA [ 34 – 36 ]. Furthermore, 11-cis retinol and 11-cis retinaldehyde as its ligands, RLBP1 is expressed in the RPE cells and Müller cells [ 37 ].…”

The Role of Vitamin A in Retinal Diseases

“…Pathogenic variants in the RLBP1 gene prevent regeneration of 11-cis-retinal, which leads to reduced autofluorescence signal [87,159]. They have been associated with a number of autosomal recessive retinal dystrophies, including RP, fundus albipunctatus, Bothnia dystrophy, Newfoundland rod-cone dystrophy and retinitis punctata albescens [150,159,160]. The latter has been linked by pathogenic variants in five different genes, whereas the RLBP1 gene is the most frequently associated with retinitis punctata albescens [161].…”

“…Atrophy of the RPE appears mid-peripherally and progressively enlarge towards the centre. Macular involvement is frequent [156,160,162,163]. Dark adaptation is always abnormal and occurs even prior retinal degeneration [159,162].…”