Mutations in the gene coding for guanylate cyclase-activating protein 2 (<Emphasis Type="Italic">GUCA1B</Emphasis> gene) in patients with autosomal dominant retinal dystrophies

Background We investigated mutations in the gene coding for guanylate-cyclase activating protein 2 (GCAP2), also known as GUCA1B gene, in Japanese patients with retinitis pigmentosa (RP) and tried to identify phenotypic characteristics associated with mutations in the gene.Subjects and methods Genomic DNA samples from 63 unrelated patients with autosomal dominant retinitis pigmentosa (ADRP) and 33 patients with autosomal recessive retinitis pigmentosa (ARRP) were screened by single-strand conformational polymorphism analysis followed by direct sequencing. Clinical features associated with a mutation were demonstrated by visual acuity, visual field testing, fundus photography, and electroretinography.Results A novel transitional mutation converting GGA to AGA at codon 157 (G157R) was identified. This mutation has been found in three index patients from three independent families. Phenotypic examination of seven members of the three families revealed that this mutation was associated with RP with or without macular involvement in five members, macular degeneration in one member, and asymptomatic normal phenotype in one member. In addition, previously unknown polymorphic changes including V29V, Y57Y, T87I, and L180L were identified.Conclusions A racial difference exists in the spectrum of mutations and/or polymorphisms in the GCAP 2 gene between British and Japanese populations. Our findings suggest that the mutation in the GCAP 2 gene can cause one form of autosomal dominant retinal dystrophy, with variable phenotypic expression and incomplete penetrance.