title: Mutation of the FOXC2 gene in familial distichiasis.
abstract: OBJECTIVE
  To examine the FOXC2 gene in a family with hereditary distichiasis.
  
  
  BACKGROUND
  Distichiasis, ie, a second row of eyelashes arising from the meibomian glands of the eyelids, can be inherited either alone (Online Mendelian Inheritance in Man [OMIM] no. 126300) or, more commonly, as part of the lymphedema-distichiasis (LD) syndrome (OMIM no. 153400). More than 45 families with mutations in the FOXC2 gene and LD have been described. Both lymphedema and distichiasis are highly penetrant. Distichiasis without lymphedema is not commonly seen.
  
  
  METHODS
  We examined three generations of a family (N = nine members) with hereditary distichiasis but without lymphedema or other features of LD syndrome. The FOXC2 gene was polymerase chain reaction--amplified from genomic DNA from all family members and examined for mutations.
  
  
  RESULTS
  Clinical examination showed distichiasis of all four lids in two affected family members across two generations. There were no other consistent ophthalmologic abnormalities in the family. A cytosine-to-adenine transversion was identified in DNA from affected study participants at nucleotide position 1076, which would be predicted to cause truncation of the protein at codon 359. This change was not observed in any of the nine unaffected family members participating.
  
  
  CONCLUSIONS
  This finding suggests that hereditary distichiasis and LD may not be separate genetic disorders but different phenotypic expressions of the same underlying disorder. Ophthalmologists should be aware that LD may present as distichiasis alone and counsel and refer their patients appropriately.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Susan L
authors.initials: SL
authors.lastname: Dagenais
authors.forename: Christine C
authors.initials: CC
authors.lastname: Nelson
authors.forename: Michael W
authors.initials: MW
authors.lastname: Glynn
authors.forename: Mark S
authors.initials: MS
authors.lastname: Caulder
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Downs
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Glover
mesh_terms: D000225:Adenine; D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics; D003062:Codon / Q000235:genetics; D003596:Cytosine; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005140:Eyelashes / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D003596:Cytosine; D000225:Adenine