title: Identification of two novel mutations in families with X-linked ocular albinism.
abstract: OBJECTIVE
  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.affiliation: Retinal Degeneration and Ophthalmic Genetics Service, Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Gallaher
authors.forename: Janda
authors.initials: J
authors.lastname: Buchholz
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Jennings
authors.forename: Maureen
authors.initials: M
authors.lastname: Neitz
authors.forename: D J
authors.initials: DJ
authors.lastname: Sidjanin
mesh_terms: D000293:Adolescent; D000328:Adult; D016117:Albinism, Ocular; D019943:Amino Acid Substitution; D003545:Cysteine; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005998:Glycine; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D014430:Twins, Monozygotic
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins; D003545:Cysteine; D005998:Glycine