title: A five generation family with a novel mutation in FOXC2 and lymphedema worsening to hydrops in the youngest generation.
abstract: We describe a five generation family with dominantly inherited lymphedema, but no distichiasis, in which 3/3 affected offspring in the fifth generation have died of fetal hydrops and related birth defects. Mutational analysis disclosed a novel mutation in FOXC2 (R121C) in affected members. We searched for possible genetic influences on the greater severity of lymphedema (hydrops) in the fifth generation. Karyotypes disclosed an extra band in Xp in one affected fetus, but this was also found in the mother. Copy number variation (CNV) studies on four members of the pedigree (mother of the three severely affected fetuses/infants; one severely affected; a full, and a half, unaffected sibs) did not detect the source of the Xp band or a possible influence on the severe phenotype. However, use of SNP arrays did allow identification of the portion of the maternal proximal Xp shared by a hydrops-affected daughter and son which was not shared by an unaffected daughter from the same sibship.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK.
authors.forename: Carole
authors.initials: C
authors.lastname: Sargent
authors.forename: Julien
authors.initials: J
authors.lastname: Bauer
authors.forename: Muhamed
authors.initials: M
authors.lastname: Khalil
authors.forename: Parker
authors.initials: P
authors.lastname: Filmore
authors.forename: Michael
authors.initials: M
authors.lastname: Bernas
authors.forename: Marlys
authors.initials: M
authors.lastname: Witte
authors.forename: M Peggy
authors.initials: MP
authors.lastname: Pearson
authors.forename: Robert P
authors.initials: RP
authors.lastname: Erickson
mesh_terms: D056915:DNA Copy Number Variations; D004487:Edema / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008209:Lymphedema / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: D051858:Forkhead Transcription Factors; C082078:mesenchyme fork head 1 protein
keywords: FOXC2; Xp; fetal hydrops; lymphedema; lymphedema distichiasis