title: Eight previously unidentified mutations found in the OA1 ocular albinism gene.
abstract: BACKGROUND
  Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene.
  
  
  METHODS
  The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments.
  
  
  RESULTS
  We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found.
  
  
  CONCLUSIONS
  The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand.
authors.affiliation: EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, CEntre de Recherches Thérapeutiques en Ophtalmologie, Université René Descartes-Paris V, Faculté de Médecine René Descartes-Site Necker, Paris, France. mayeur@necker.fr
authors.forename: Hélène
authors.initials: H
authors.lastname: Mayeur
authors.forename: Olivier
authors.initials: O
authors.lastname: Roche
authors.forename: Christelle
authors.initials: C
authors.lastname: Vêtu
authors.forename: Carolina
authors.initials: C
authors.lastname: Jaliffa
authors.forename: Dominique
authors.initials: D
authors.lastname: Marchant
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Francis L
authors.initials: FL
authors.lastname: Munier
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: Alex V
authors.initials: AV
authors.lastname: Levin
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.forename: Joanne
authors.initials: J
authors.lastname: Sutherland
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Edith
authors.initials: E
authors.lastname: Said
authors.forename: Eedy
authors.initials: E
authors.lastname: Mezer
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dufier
authors.forename: Cécile
authors.initials: C
authors.lastname: Marsac
authors.forename: Maurice
authors.initials: M
authors.lastname: Menasche
authors.forename: Marc
authors.initials: M
authors.lastname: Abitbol
mesh_terms: D016117:Albinism, Ocular / Q000235:genetics*; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D022821:RNA Splice Sites; D017384:Sequence Deletion
chemical_list: D005136:Eye Proteins; C095276:GPR143 protein, human; D008562:Membrane Glycoproteins; D022821:RNA Splice Sites