title: Screening for mutations of Axenfeld-Rieger syndrome caused by FOXC1 gene in Japanese patients.
abstract: OBJECTIVE
  Mutations in the forkhead transcription factor gene (FOXC1) have been recently shown to cause some cases of juvenile glaucoma associated with a variety of anterior-segment anomalies. The purpose of this study was to investigate the clinical features of Axenfeld-Rieger syndrome caused by FOXC1 mutations in Japanese patients.
  
  
  METHODS
  After informed consent was obtained, genomic DNA was isolated from peripheral blood. The DNA-sequence changes were analyzed using single-strand conformation polymorphism analysis and automated sequencing in six Japanese probands with Axenfeld-Rieger syndrome.
  
  
  RESULTS
  The authors identified four mutations: pedigree 1 (26-47ins22), 2 (Ile91Ser), 3 (286ins1), and 4 (Arg127His). Two pedigrees showed new mutations in FOXC1. In pedigrees 1,2, and 4, younger generations had iris hypoplasia with severe early-onset glaucoma, whereas their parents had posterior embryotoxon without glaucoma. Pedigree 3 had a single affected person with iris hypoplasia and posterior embryotoxon with a mild increase of intraocular pressure.
  
  
  CONCLUSIONS
  Four different FOXC1 mutations were found in four of six Japanese pedigrees with Axenfeld-Rieger syndrome. This was a new mutation in two pedigrees that was not found in earlier generations. This study confirms that mutations in this gene cause maldevelopment of the anterior segment of the eye.
authors.affiliation: Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kawase
authors.forename: K
authors.initials: K
authors.lastname: Kawase
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: K
authors.initials: K
authors.lastname: Sugiyama
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kitazawa
authors.forename: W L
authors.initials: WL
authors.lastname: Alward
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
authors.forename: D Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000869:Anterior Eye Segment / Q000002:abnormalities*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005124:Eye Abnormalities / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D005260:Female; D051858:Forkhead Transcription Factors; D005901:Glaucoma / Q000208:ethnology / Q000235:genetics* / Q000601:surgery; D006801:Humans; D007223:Infant; D007429:Intraocular Pressure; D007498:Iris / Q000002:abnormalities*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors