title: Lymphoedema-distichiasis and FOXC2: unreported mutations, de novo mutation estimate, families without coding mutations.
abstract: Lymphoedema-distichiasis (LD) is a syndromic form of primary lymphoedema, where mutations in the gene for the developmental transcription factor FOXC2 have been shown to be causative. The disorder has been considered very rare, but our group has now ascertained 34 families and 11 sporadic cases in the UK. Two families with LD have no mutation in the coding region of FOXC2, although both are consistent with linkage to the FOXC2 locus. A deletion has been ruled out as a possible cause of LD in these families, leaving promoter mutations as the most likely cause. Sixteen previously unpublished mutations are reported, plus an estimate of the frequency of new mutations in this disorder.
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Medical School, Cranmer Terrace, Tooting, London, SW17 ORE, UK. sggt100@sghms.ac.uk
authors.forename: Carolyn
authors.initials: C
authors.lastname: Sholto-Douglas-Vernon
authors.forename: Rachel
authors.initials: R
authors.lastname: Bell
authors.forename: Glen
authors.initials: G
authors.lastname: Brice
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
authors.forename: Anne H
authors.initials: AH
authors.lastname: Child
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
authors.forename: Russell
authors.initials: R
authors.lastname: Mellor
authors.forename: Kevin
authors.initials: K
authors.lastname: Burnand
authors.forename: Peter
authors.initials: P
authors.lastname: Mortimer
authors.forename: Steve
authors.initials: S
authors.lastname: Jeffery
mesh_terms: D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D051858:Forkhead Transcription Factors; D005787:Gene Frequency; D008040:Genetic Linkage; D006801:Humans; D008209:Lymphedema / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics*; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D006113:United Kingdom
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein