title: Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer.
abstract: We report the association of CDH1/E-cadherin mutations with cleft lip, with or without cleft palate (CLP), in two families with hereditary diffuse gastric cancer (HDGC). In each family, the CDH1 mutation was a splicing mutation generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant negative effects. We found that CDH1 is highly expressed at 4 and 5 weeks in the frontonasal prominence, and at 6 weeks in the lateral and medial nasal prominences of human embryos, and is therefore expressed during the critical stages of lip and palate development. These findings suggest that alteration of the E-cadherin pathway can contribute to human clefting.
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.
authors.forename: T
authors.initials: T
authors.lastname: Frebourg
authors.forename: C
authors.initials: C
authors.lastname: Oliveira
authors.forename: P
authors.initials: P
authors.lastname: Hochain
authors.forename: R
authors.initials: R
authors.lastname: Karam
authors.forename: S
authors.initials: S
authors.lastname: Manouvrier
authors.forename: C
authors.initials: C
authors.lastname: Graziadio
authors.forename: M
authors.initials: M
authors.lastname: Vekemans
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: S
authors.initials: S
authors.lastname: Baert-Desurmont
authors.forename: C
authors.initials: C
authors.lastname: Alexandre
authors.forename: S
authors.initials: S
authors.lastname: Lejeune Dumoulin
authors.forename: C
authors.initials: C
authors.lastname: Marroni
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Castedo
authors.forename: M
authors.initials: M
authors.lastname: Lovett
authors.forename: J
authors.initials: J
authors.lastname: Winston
authors.forename: J C
authors.initials: JC
authors.lastname: Machado
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: E W
authors.initials: EW
authors.lastname: Jabs
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.forename: Ph
authors.initials: P
authors.lastname: Pellerin
authors.forename: J P
authors.initials: JP
authors.lastname: Triboulet
authors.forename: M
authors.initials: M
authors.lastname: Scotte
authors.forename: F
authors.initials: F
authors.lastname: Le Pessot
authors.forename: A
authors.initials: A
authors.lastname: Hedouin
authors.forename: F
authors.initials: F
authors.lastname: Carneiro
authors.forename: M
authors.initials: M
authors.lastname: Blayau
authors.forename: R
authors.initials: R
authors.lastname: Seruca
mesh_terms: D000328:Adult; D015820:Cadherins / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D015820:Cadherins