title: Molecular Analysis of NOTCH2 in Patients with Primary Open-Angle Glaucoma.
abstract: OBJECTIVE
  Transgenic mice overexpressing Notch2 in the uvea exhibit a hyperplastic ciliary body leading to increased IOP and glaucoma. The aim of this study was to investigate the possible presence of NOTCH2 variants in patients with primary open-angle glaucoma (POAG).
  
  
  METHODS
  We screened DNA samples from 130 patients with POAG for NOTCH2 variants by denaturing high-performance liquid chromatography after PCR amplification and validated our data by direct Sanger sequencing.
  
  
  RESULTS
  No mutations were observed in the coding regions of NOTCH2 or in the splice sites. 19 known SNPs (single nucleotide polymorphisms) were detected. An SNP located in intron 24, c.[4005+45A>G], was seen in 28.5% of the patients (37/130 patients). As this SNP is reported to have a minor allele frequency of 7% in the 1000 genomes database, it could be associated with POAG. However, we evaluated its frequency in an ethnic-matched control group of 96 subjects unaffected by POAG and observed a frequency of 29%, indicating that it was not related to POAG.
  
  
  CONCLUSIONS
  NOTCH2 seemed to be a good candidate for POAG as it is expressed in the anterior segment in the human eye. However, mutational analysis did not show any causative mutation. This study also shows that proper ethnic-matched control groups are essential in association studies and that values given in databases are sometimes misleading.
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Jakobsson
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Kheir
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.affiliation: IRO-Institute for Research in Ophthalmology, Sion, Switzerland.
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
mesh_terms: D000818:Animals; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005901:Glaucoma; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051883:Receptor, Notch2 / Q000235:genetics*
chemical_list: C497764:NOTCH2 protein, human; D051883:Receptor, Notch2