Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens

PURPOSE. To determine the frequency and spectrum of mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein (CRALBP) in patients w ith hereditary retinal degeneration. METHODS. The single-strand conformation polymorphism (SSCP) technique and a direct genomic sequencing technique were used to screen the coding exons o f this gene (exons 2-8) for mutations in 324 unrelated patients with recess ive or isolate retinitis pigmentosa, retinitis punctata albescens, Leber co ngenital amaurosis, or a related disease. Variant DNA fragments revealed by SSCP analysis were subsequently sequenced. Selected alleles that altered t he coding region or intron splice sites were evaluated further through segr egation analysis in the families of the index cases. RESULTS. Four novel mutations were identified in this gene among three unre lated patients with recessively inherited retinitis punctata albescens. Two of the mutations were missense: one was a frameshift, and one affected a c anonical splice donor site. CONCLUSIONS,us. Recessive mutations in the RLBP1 gene are an uncommon cause of retinal degeneration in humans. The phenotype produced by RLBP1 mutatio ns seems to be a form of retinitis punctata albescens.