title: Probable exclusion of GLC1A as a candidate glaucoma gene in a family with middle-age-onset primary open-angle glaucoma.
abstract: OBJECTIVE
  To determine whether an adult-onset variety of primary open-angle glaucoma in family UM:POAG1 is linked to the previously mapped GLC1A juvenile-onset primary open-angle glaucoma locus on chromosome 1q or whether linkage can be excluded.
  
  
  METHODS
  Microsatellite repeat markers from the 9 cM D1S196 to D1S218 interval containing the GLC1A gene were amplified by polymerase chain reaction from DNA samples collected from 11 members of one sibship in family UM:POAG1. Haplotype analysis was carried out, including calculation of the probability that the observed data would have been obtained if the underlying cause of primary open-angle glaucoma in this family were a defect in a gene located in the tested interval. Linkage analysis was carried out under an autosomal dominant model for GLC1A glaucoma.
  
  
  RESULTS
  In family UM:POAG1, primary open-angle glaucoma was diagnosed in six surviving and one deceased member of a sibship of 13 individuals during the fifth or sixth decade of life. Glaucoma in this family has a later average age at diagnosis and significantly less elevation in intraocular pressure than GLC1A glaucoma so far described. Haplotype analysis, using a population prevalence up to 0.9%, shows that it is unlikely that the reported data would have been observed if primary open-angle glaucoma in this pedigree were due to the GLC1A locus on chromosome 1q21-q31. Linkage analysis under the juvenile glaucoma autosomal dominant model allowed exclusion of linkage across the entire GLC1A genetic inclusion interval, with a maximum lod score in the interval of -3.28.
  
  
  CONCLUSIONS
  The most likely interpretation of these observations is that a defect in the GLC1A glaucoma gene is not responsible for adult-onset primary open-angle glaucoma in family UM:POAG1. This suggests the existence of at least two primary open-angle glaucoma genes, the previously reported GLC1A gene on chromosome 1q and another gene located elsewhere in the genome. Diagnosis of UM:POAG1 glaucoma between 42 and 57 years of age also raises questions regarding the relation of the glaucoma present in this family to the common later-age-onset form of the disease.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Richards
authors.forename: P R
authors.initials: PR
authors.lastname: Lichter
authors.forename: S
authors.initials: S
authors.lastname: Herman
authors.forename: E R
authors.initials: ER
authors.lastname: Hauser
authors.forename: Y C
authors.initials: YC
authors.lastname: Hou
authors.forename: A T
authors.initials: AT
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Boehnke
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004276:DNA, Satellite / Q000032:analysis; D005190:Family; D005260:Female; D005796:Genes; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D010375:Pedigree; D016133:Polymerase Chain Reaction
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers