title: Genetic analysis of an Indian family with members affected with juvenile-onset primary open-angle glaucoma.
abstract: OBJECTIVE
  Glaucoma is the second leading cause of blindness. In India, approximately 1.5 million people are blind due to glaucoma. Mutations in the MYOC gene located at the GLC1A locus on chromosome 1q21-q31 have been found in patients with juvenile-onset primary open-angle glaucoma (J-POAG). The purpose of the present study was to identify the genetic cause of glaucoma in a four-generation Indian family affected with J-POAG.
  
  
  METHODS
  Peripheral blood samples were obtained from individuals for genomic DNA isolation. To determine if this family was linked to the GLC1A locus, haplotyping analysis was carried out using microsatellite markers from the GLC1A candidate region. Exon-specific primers from exon 3 of the MYOC gene were used to amplify DNA samples from individuals. Mutation analysis was carried out using PCR-SSCP and DNA sequence analyses.
  
  
  RESULTS
  Pedigree analysis suggested that glaucoma in this family segregated as an autosomal dominant trait. Of six patients, five had J-POAG and one had adult-onset POAG (A-POAG). Haplotype analysis suggested linkage of this family to the GLC1A locus. Mutation and sequence analyses showed a novel missense mutation, c.821C > G (p.P274R), in the C-terminal olfactomedin domain coded by exon 3 of the MYOC gene. One patient was found to be homozygous for this mutation with a severe phenotype.
  
  
  CONCLUSIONS
  This study reports a novel missense mutation in a four-generation Indian family with all but one member affected with J-POAG. The total number of mutations described so far in the MYOC gene, including the one reported here, is 59 with a clustering of 52 mutations in exon 3.
authors.affiliation: Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
authors.forename: M
authors.initials: M
authors.lastname: Markandaya
authors.forename: T K
authors.initials: TK
authors.lastname: Ramesh
authors.forename: V
authors.initials: V
authors.lastname: Selvaraju
authors.forename: Syril K
authors.initials: SK
authors.lastname: Dorairaj
authors.forename: Ravi
authors.initials: R
authors.lastname: Prakash
authors.forename: Jyoti
authors.initials: J
authors.lastname: Shetty
authors.forename: A
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin