Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer

• Published in: Journal of medical genetics Vol. 43; no. 2; pp. 138 - 142
• Main Authors: Frebourg, T, Oliveira, C, Hochain, P, Karam, R, Manouvrier, S, Graziadio, C, Vekemans, M, Hartmann, A, Baert-Desurmont, S, Alexandre, C, Lejeune Dumoulin, S, Marroni, C, Martin, C, Castedo, S, Lovett, M, Winston, J, Machado, J C, Attié, T, Jabs, E W, Cai, J, Pellerin, Ph, Triboulet, J P, Scotte, M, Le Pessot, F, Hedouin, A, Carneiro, F, Blayau, M, Seruca, R
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-02-2006; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Adult; Age; Biological and medical sciences; Biopsy; Cadherins - genetics; Cardiology. Vascular system; CDH1/E-cadherin; Cell adhesion; Cell adhesion & migration; CL, cleft lip; cleft lip; Cleft Lip - genetics; cleft lip with or without cleft palate; Cleft lip/palate; Cleft Palate - genetics; CLP; CLP, cleft lip with or without cleft palate; COGENE; COGENE, Craniofacial and Oral Gene Expression Network Consortium; Craniofacial and Oral Gene Expression Network Consortium; Developmental stages; DNA Mutational Analysis; E-cadherin; Embryos; Endoscopy; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Gastric cancer; Gene deletion; Gene expression; Gene Expression Profiling; General aspects. Genetic counseling; HDGC; HDGC, hereditary diffuse gastric cancer; hereditary diffuse gastric cancer; Humans; Medical genetics; Medical sciences; Metastasis; Mutation; Mutation - genetics; NMD; NMD, nonsense mediated decay; Non tumoral diseases; nonsense mediated decay; Otorhinolaryngology. Stomatology; Pedigree; Proteins; Short Report; Short reports; Stomach Neoplasms - genetics; Diffuse; Human; Cleft palate; Cleft lip; Stomatology; Family study; Congenital cleft; Malignant tumor; Hereditary; Congenital disease; Stomach cancer; Malformation; Family environment; Digestive diseases; Genetics; Oral cavity disease; Mutation; E Cadherin; Gastric disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2005.031385

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.