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 cau sing a type of retinitis punctata albescens, called Bothnia dystrophy, foun d 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. Direc t genomic sequencing of the gene encoding cellular retinaldehyde-binding pr otein was performed after the linkage analysis had been completed. RESULTS. Affected individuals showed night blindness from early childhood w ith features consistent with retinitis punctata albescens and macular degen eration. The responsible gene was mapped to 15q26, the same region to which the cellular retinaldehyde-binding protein gene has been assigned. Subsequ ent analysis showed all affected patients were homozygous for a C to T subs titution in exon 7 of the same gene, leading to the missense mutation Arg23 4Trp. Analysis of marker haplotypes suggested that all cases had a common a ncestor who carried the mutation. CONCLUSIONS. A missense mutation in the cellular retinaldehyde-binding prot ein 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.