Ocular phenotype of bothnia dystrophy, an autosomal recessive retinitis pigmentosa associated with an R234W mutation in the RLBP1 gene.

OBJECTIVE: To describe the phenotype of Bothnia dystrophy, an autosomal recessive retinal dystrophy with an R234W mutation in the RLBP1 gene encoding cellular retinaldehyde-binding protein. DESIGN: Medical records were reviewed retrospectively. Ophthalmologic examination, including kinetic perimetry and, in selected cases, adaptometry, color vision tests, fluorescein angiography, and electrophysiologic studies, was performed. The study included 24 individuals, all homozygous for an R234W mutation in the RLBP1 gene. RESULTS: Patients typically show night blindness from early childhood. In young adults, retinitis punctata albescens was observed, followed by macular degeneration and a decrease in visual acuity that led to legal blindness in early adulthood. Dark adaptometry and electrophysiologic testing showed an initial loss of rod function followed by a progressive reduction of the cone responses in older ages. CONCLUSIONS: Bothnia dystrophy is a unique retinal dystrophy belonging to the rod-cone dystrophies and has a high prevalence in northern Sweden. Fifty-seven cases of Bothnia dystrophy have been diagnosed, indicating a prevalence as high as 1 per 4500 population in the geographic area studied. A defect ability of mutated cellular retinaldehyde-binding protein to bind retinoid probably explains the defect rod function followed by central and peripheral degeneration. CLINICAL RELEVANCE: Retinal dystrophies associated with other mutations of the RLBP1 gene, including retinitis pigmentosa of Bothnia type, might account for a considerable number of cases of autosomal recessive retinitis pigmentosa in other geographic areas as well.

Bothnia dystrophy caused by mutations in the cellular retinaldehyde-binding protein gene (RLBP1) on chromosome 15q26.

PURPOSE: To determine the chromosomal location and to identify the gene causing a type of retinitis punctata albescens, called Bothnia dystrophy, found in a restricted geographic area in northern Sweden. METHODS: Twenty patients from seven families originating from a restricted geographic area in northern Sweden were clinically examined. Microsatellite markers were analyzed in all affected and unaffected family members. Direct genomic sequencing of the gene encoding cellular retinaldehyde-binding protein was performed after the linkage analysis had been completed. RESULTS: Affected individuals showed night blindness from early childhood with features consistent with retinitis punctata albescens and macular degeneration. The responsible gene was mapped to 15q26, the same region to which the cellular retinaldehyde-binding protein gene has been assigned. Subsequent analysis showed all affected patients were homozygous for a C to T substitution in exon 7 of the same gene, leading to the missense mutation Arg234Trp. Analysis of marker haplotypes suggested that all cases had a common ancestor who carried the mutation. CONCLUSIONS: A missense mutation in the cellular retinaldehyde-binding protein gene is the cause of Bothnia dystrophy. The disease is a local variant of retinitis punctata albescens that is common in northern Sweden due to a founder mutation.