title: Osteogenesis imperfecta and primary open angle glaucoma: genotypic analysis of a new phenotypic association.
abstract: OBJECTIVE
  Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG.
  
  
  METHODS
  Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC).
  
  
  RESULTS
  All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452-2A>T or IVS36-2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC.
  
  
  CONCLUSIONS
  We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Wallace
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Chau
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Santiago-Turla
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC ; Duke University Center for Human Genetics, Durham, NC.
authors.forename: Michael
authors.initials: M
authors.lastname: Hauser
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Pratap
authors.initials: P
authors.lastname: Challa
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC.
authors.forename: Leon W
authors.initials: LW
authors.lastname: Herndon
authors.affiliation: Department of Ophthalmology, Duke Eye Center, Durham, NC ; Duke University Center for Human Genetics, Durham, NC.
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
mesh_terms: D000368:Aged; D018389:Codon, Nonsense; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D003598:Cytoskeletal Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005902:Glaucoma, Open-Angle / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009900:Optic Nerve / Q000473:pathology; D010013:Osteogenesis Imperfecta / Q000150:complications* / Q000235:genetics*; D022821:RNA Splice Sites; D017384:Sequence Deletion; D014794:Visual Fields; D000099179:Myocilin
chemical_list: D018389:Codon, Nonsense; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D022821:RNA Splice Sites; D000099179:Myocilin