title: Lymphedema-distichiasis syndrome and FOXC2 gene mutation.
abstract: OBJECTIVE
  To describe the clinical characteristics of a family with autosomal dominant lymphedema-distichiasis syndrome and to report the results of analysis of the FOXC2 gene
  
  
  METHODS
  Observational and experimental study.
  
  
  METHODS
  The setting was a clinical practice. The study population was 17 members of a family with lymphedema-distichiasis. Observation procedures were complete ophthalmologic examinations and collection of blood samples. DNA was extracted. Mutation analysis of the coding region of the FOXC2 gene was performed using direct sequencing of polymerase chain reaction (PCR) product and a restriction enzyme assay. The main outcome measure was inheritance of mutation in FOXC2 gene.
  
  
  RESULTS
  Nine patients had distichiasis or lymphedema or both and eight did not. Sequencing of the coding region of the only translated exon of the FOXC2 gene revealed a C to A transversion at position 939 resulting in a Tyr313Stop codon with premature termination of translation and a truncated protein product. The mutation was present in all nine affected individuals and in an asymptomatic 9-year-old boy.
  
  
  CONCLUSIONS
  Distichiasis-lymphedema syndrome results from mutations in FOXC2, a member of the forkhead/winged family of transcription factors. There is intrafamilial variation in the clinical expression of the mutation.
authors.affiliation: Center for Genetic Eye Diseases, Cole Eye Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Khouloud
authors.initials: K
authors.lastname: Al-Khayer
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kimak
authors.forename: Susan
authors.initials: S
authors.lastname: Crowe
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wilson
authors.forename: David N
authors.initials: DN
authors.lastname: Finegold
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: David M
authors.initials: DM
authors.lastname: Meisler
mesh_terms: D001483:Base Sequence; D002648:Child; D000013:Congenital Abnormalities / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005140:Eyelashes / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D008209:Lymphedema / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein