Identification of two novel mutations in families with X-linked ocular albinism.
PURPOSE: Our goal was to evaluate the OA1 gene, also known as G-protein coupled receptor 143 (GPR143), in two United States families, one from the mid-west and one from the mid-south, who had clinical features of X-linked ocular albinism. Both families had previously tested negative for mutations. METHODS: Selected family members underwent a detailed ophthalmologic evaluation. Blood samples were obtained, and genomic DNA isolated. Mutational analysis by direct sequencing was used to evaluate OA1 exons and intron/exon junction. RESULTS: Ophthalmic features in the evaluated family members were consistent with X-linked ocular albinism. Mutation screening and sequence analysis of the OA1 gene in the mid-west family identified a novel 190delC deletion. The 190delC mutation was predicted to result in a frameshift following Ser63, an addition of 16 novel amino acids and a premature stop. In the mid-south family, a 346T>G substitution was identified in exon 2. The 346T>G mutation was predicted to result in a substitution of the highly conserved Cys116 to Gly and disruption of the disulfide bridge essential for the normal structure and function of the OA1 protein. CONCLUSIONS: Two novel mutations in the OA1 gene were identified in two families with ocular albinism. The identified mutations are likely loss-of-function mutations. These findings confirm that mutations in the OA1 gene are associated with the majority of X-linked ocular albinism cases.
Iannaccone, A; Gallaher, KT; Buchholz, J; Jennings, BJ; Neitz, M; Sidjanin, DJ
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