title: A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene.
abstract: OBJECTIVE
  Mutations of the forkhead transcription factor gene FOXC1 result in anterior segment anomalies. No description of the spectrum of defects resulting from a single point mutation of this gene exists in the ophthalmology literature. We have screened all available patients with Axenfeld-Rieger genes (PITX2 and FOXC1). In this report, we clinically characterize the spectrum of ocular and systemic manifestations in one family resulting from a previously reported point mutation (Phe112Ser) in FOXC1.
  
  
  METHODS
  Observational case series.
  
  
  METHODS
  Ten members of a multigenerational family were examined for signs of glaucoma, anterior segment abnormalities, and systemic features of Axenfeld-Rieger syndrome. The examinations were performed in an ophthalmology examination room or in the patients' homes. Blood was obtained from 10 members and screened for mutations in FOXC1 using direct DNA sequencing.
  
  
  RESULTS
  A single mutation causing a T to C change in codon 112 (Phe112Ser) of FOXC1 was present in six members of the family. Five of these six patients were examined and all demonstrated anterior segment anomalies. One patient had Axenfeld anomaly, one had Rieger syndrome, and one had both Axenfeld anomaly and Peters anomaly. Additionally, some members demonstrated cardiac abnormalities, which may be secondary to their FOXC1 mutation.
  
  
  CONCLUSIONS
  A wide spectrum of clinical phenotypes can result from a single point mutation of FOXC1. This report confirms that Rieger syndrome (with dental and facial abnormalities) can be caused by a mutation in FOXC1. It is also the first report of Peters anomaly being caused by a FOXC1 mutation.
authors.affiliation: Department of Ophthalmology, Howard Hughes Medical Institute, The University of Iowa, Iowa City, Iowa, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Honkanen
authors.forename: Darryl Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Swiderski
authors.forename: Steven R
authors.initials: SR
authors.lastname: Bennett
authors.forename: Sungpyo
authors.initials: S
authors.lastname: Hong
authors.forename: Young H
authors.initials: YH
authors.lastname: Kwon
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Wallace L M
authors.initials: WL
authors.lastname: Alward
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000869:Anterior Eye Segment / Q000002:abnormalities*; D002648:Child; D003318:Corneal Opacity / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005124:Eye Abnormalities / Q000235:genetics*; D005147:Facial Bones / Q000002:abnormalities; D005260:Female; D051858:Forkhead Transcription Factors; D005901:Glaucoma / Q000235:genetics; D006801:Humans; D007498:Iris / Q000002:abnormalities*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D013577:Syndrome; D014071:Tooth Abnormalities / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors