Identification of two novel mutations in families with X-linked ocular albinism.

Abstract

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.

• Authors: Alessandro Iannaccone, Kevin T Gallaher, Janda Buchholz, Barbara J Jennings, Maureen Neitz, D J Sidjanin
• Journal: Molecular vision (Mol Vis) Vol. 13 Pg. 1856-61 (Oct 02 2007) ISSN: 1090-0535 [Electronic] United States
• PMID: 17960122 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• GPR143 protein, human
• Membrane Glycoproteins
• Cysteine
• Glycine

Topics

• Adolescent
• Adult
• Albinism, Ocular
• Amino Acid Substitution
• Cysteine
• Eye Proteins (genetics)
• Female
• Gene Deletion
• Genetic Diseases, X-Linked (complications, genetics, pathology, physiopathology)
• Glycine
• Humans
• Male
• Membrane Glycoproteins (genetics)
• Mutation
• Pedigree
• Twins, Monozygotic