Mutations in RLBP1 associated with fundus albipunctatus in consanguineous Pakistani families

Abstract

Objective To identify disease-causing mutations in two consanguineous Pakistani families with fundus albipunctatus. Methods Affected individuals in both families underwent a thorough clinical examination including funduscopy and electroretinography. Blood samples were collected from all participating members and genomic DNA was extracted. Exclusion analysis was completed with microsatellite short tandem repeat markers that span all reported loci for fundus albipunctatus. Two-point logarithm of odds (LOD) scores were calculated, and coding exons and exon–intron boundaries of RLBP1 were sequenced bi-directionally. Results The ophthalmic examination of affected patients in both families was consistent with fundus albipunctatus. The alleles of markers on chromosome 15q flanking RLBP1 segregated with the disease phenotype in both families and linkage was further confirmed by two-point LOD scores. Bi-directional sequencing of RLBP1 identified a nonsense mutation (R156X) and a missense mutation (G116R) that segregated with the disease phenotype in their respective families. Conclusions These results strongly suggest that mutations in RLBP1 are responsible for fundus albipunctatus in the affected individuals of these consanguineous Pakistani families.

Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

“…A similar fundus phenotype has also been described in young patients with Bothnia dystrophy associated with mutations in RLBP1 (Katsanis et al, 2001;Naz et al, 2011) (Table 1.14). In the early stages the white dots may be indistinguishable from those in FA but there is typical progression characterised by scalloped areas of atrophy that eventually encroach upon the posterior pole and there may be intra-retinal pigment migration.…”

“…10; Tables 1.14 and 1.15; see 2. Phenotypic characteristics of CSNB) (Katsanis et al, 2001;Naz et al, 2011;Schatz et al, 2011). To date, most of the mutations leading to the Schubert-Bornschein phenotype have been identified in CAC-NA1F and NYX (Tables 1.10 and 1.5, Figs.…”

CRALBP supports the mammalian retinal visual cycle and cone vision

“…In mammals, CRALBP is encoded by a single gene, Rlbp1, expressed in both RPE and Müller cells. Mutations in human RLBP1 cause several autosomal recessive retinal diseases, such as autosomal recessive retinitis pigmentosa (13), Bothnia dystrophy (14)(15)(16), retinitis punctata albescens (17), fundus albipunctatus (18,19), and Newfoundland rod-cone dystrophy (20). These visual disorders are characterized by early-onset night blindness and may be followed by functional defects in the macular region (21).…”

Article A case of fundus albipunctatus in both eyes

“…Mostly, mutations in the RDH5 gene [6] (11-cis retinol dehydrogenase) affected retinoid metabolism (11-cis retinol dehydrogenase) in the visual cycle, leading to FA features. However, other genes mutation had been reported, as the RLBP1 gene [7] (retinaldehyde binding protein 1) and RPE65 gene [8] (RPE-specific protein). 11-cis retinol dehydrogenase, produced in the smooth endoplasmic reticulum of the pigment epithelium cells, has revealed great importance in the visual cycle and the production and accumulation of lipofuscin in the pigment epithelium cells.…”