title: Role of MYOC and OPTN sequence variations in Spanish patients with primary open-angle glaucoma.
abstract: OBJECTIVE
  To retrospectively investigate the contribution of myocilin (MYOC) and optineurin (OPTN) sequence variations to adult-onset ocular hypertension (OHT) and primary open-angle glaucoma (POAG) in Spanish patients.
  
  
  METHODS
  The promoter region and the three exons of MYOC were analyzed by direct PCR DNA sequencing in 40 OHT and 110 POAG unrelated patients. We used 98 subjects in whom OHT or glaucoma had been ruled out as controls. We also screened the complete coding region of the OPTN gene (exons 4-16) in all subjects by single-stranded conformational polymorphisms (SSCPs).
  
  
  RESULTS
  We identified six common single nucleotide polymorphisms (SNPs) in the promoter region of MYOC (-1000C>G, -387C>T, -306G>A, -224T>C, -126T>C and -83G>A) and a polymorphic GT microsatellite (-339(GT)11-19). In addition, we detected four novel, rare DNA polymorphisms. None of these DNA sequence variations were associated with either OHT or POAG. We also found three (2.7%) POAG patients with MYOC pathogenic mutations. Two of these pathogenic mutations (Gln368Stop and Ala445Val) were previously described whereas the third (Tyr479His) was novel. Transient expression of the novel mutation in 293T cells supported its pathogenicity. Only two OPTN polymorphisms, which are not associated with the disease, were detected.
  
  
  CONCLUSIONS
  Overall, our data show that in Spain a minority of adult-onset high-pressure POAG patients carry heterozygous disease-causing mutations in the MYOC gene and that OPTN is not involved in either OHT or POAG.
authors.affiliation: Servicio de Oftalmología, Complejo Hospitalario Universitario de Albacete (Hospital Perpetuo Socorro), Albacete, Spain. phacos@ozu.es <phacos@ozu.es>
authors.forename: Francisco
authors.initials: F
authors.lastname: Lopez-Martinez
authors.forename: Maria-Pilar
authors.initials: MP
authors.lastname: Lopez-Garrido
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanchez-Sanchez
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Campos-Mollo
authors.forename: Miguel
authors.initials: M
authors.lastname: Coca-Prados
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009798:Ocular Hypertension / Q000235:genetics / Q000473:pathology; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics; D013030:Spain; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D044465:White People / Q000235:genetics*; D000099179:Myocilin
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human