title: Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United States.
abstract: OBJECTIVE
  Previous studies have suggested that Optineurin (OPTN) sequence variants contribute to low-tension glaucoma (LTG) in ethnically homogeneous populations. The purpose of this study is to evaluate the prevalence of OPTN sequence variants in an ethnically diverse population of LTG patients from the United States, and to describe the phenotype of patients with OPTN sequence variants preferentially found in LTG patients.
  
  
  METHODS
  Genomic DNA purified from 67 LTG patients was screened for DNA sequence variants located in the exons and flanking introns of the OPTN gene using high-performance liquid chromatography analysis and direct genomic DNA sequencing. Eighty-six primary open-angle glaucoma probands and 100 control patients were also analyzed.
  
  
  RESULTS
  Nine OPTN DNA sequence variants were identified in this patient population including the 2 previously identified heterozygous nonsynonymous single-nucleotide polymorphisms in exons 4 and 5. Four LTG patients with severe disease and positive family history of glaucoma, were found to have DNA sequence changes not found in primary open-angle glaucoma probands or control individuals including the previously reported E50K variation.
  
  
  CONCLUSIONS
  The results of this study support the rare association of OPTN sequence variants with familial forms of LTG. The E50K mutation seems to be associated with a severe form of LTG, and although rare, the identification of this sequence variant in patients at risk may help direct appropriate therapy.
authors.affiliation: Center for Human Genetics Duke School of Medicine, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Dayse Figueiredo
authors.initials: DF
authors.lastname: Sena
authors.forename: Jason
authors.initials: J
authors.lastname: Flor
authors.forename: Jeff
authors.initials: J
authors.lastname: Walter
authors.forename: Josette
authors.initials: J
authors.lastname: Auguste
authors.forename: Karen
authors.initials: K
authors.lastname: Larocque-Abramson
authors.forename: Felicia
authors.initials: F
authors.lastname: Graham
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delbono
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: R
authors.initials: R
authors.lastname: Rand Allingham
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
mesh_terms: D000328:Adult; D001213:Asian; D044383:Black People; D018797:Cell Cycle Proteins; D002851:Chromatography, High Pressure Liquid; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009798:Ocular Hypertension / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017422:Sequence Analysis, DNA; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People; D001741:Black or African American
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA