Mutation detection of OA1 gene in X-linked ocular albinism

Purpose. X-linked Nettleship-Falls ocular albinism (OA1, McKusick 300500) affects 1/150,000 males. Affected males have severely impaired vision, congenital nystagmus, photophobia with macular hypoplasia, and iris transillumination defects. The gene for OA1 has previously been mapped to the Xp22.3 region between DXS143 and DXS85 by linkage analysis. Recently the OA1 gene has been cloned and sequenced (Bassi et al, 1995). The coding region includes 9 exons. Gene mutations, including deletions, insertions, missense and splice mutations were detected. Over 1/3 of the mutations identified were large deletions. We previously performed linkage analysis in a large 5 generation pedigree with OA1 which included 43 members, of which 18 are affected and assigned the gene to the DXS85-DXS278 interval. Methods. We performed mutation analysis in this family using PCR amplification and genotype scanning of OA1 exons 1-9 (Bass et al, 1995) from genomic DNA. The results showed deletion of exons 2-8 in all affected males. Results. The large intragenic deletion of the OA1 gene in this pedigree generated the typical ocular phenotype in the eye. Conclusions. Prenatal diagnosis and carrier screening are possible using either PCR, genotype scanning or Southern blot analysis.