ZFIN ID: ZDB-PUB-180120-6
Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome
Kievit, A., Tessadori, F., Douben, H., Jordens, I., Maurice, M., Hoogeboom, J., Hennekam, R., Nampoothiri, S., Kayserili, H., Castori, M., Whiteford, M., Motter, C., Melver, C., Cunningham, M., Hing, A., Kokitsu-Nakata, N.M., Vendramini-Pittoli, S., Richieri-Costa, A., Baas, A.F., Breugem, C.C., Duran, K., Massink, M., Derksen, P.W.B., van IJcken, W.F.J., van Unen, L., Santos-Simarro, F., Lapunzina, P., Gil-da Silva Lopes, V.L., Lustosa-Mendes, E., Krall, M., Slavotinek, A., Martinez-Glez, V., Bakkers, J., van Gassen, K.L.I., de Klein, A., van den Boogaard, M.H., van Haaften, G.
Date: 2018
Source: European journal of human genetics : EJHG   26(2): 210-219 (Journal)
Registered Authors: Bakkers, Jeroen, Slavotinek, Anne
Keywords: none
MeSH Terms:
  • Adolescent
  • Adult
  • Animals
  • Antigens, CD/genetics*
  • Antigens, CD/metabolism
  • Cadherins/genetics*
  • Cadherins/metabolism
  • Catenins/genetics*
  • Catenins/metabolism
  • Cell Adhesion
  • Child
  • Child, Preschool
  • Cleft Lip/genetics*
  • Cleft Lip/pathology
  • Cleft Palate/genetics*
  • Cleft Palate/pathology
  • Ectropion/genetics*
  • Ectropion/pathology
  • Female
  • Humans
  • MCF-7 Cells
  • Male
  • Mutation*
  • Protein Binding
  • Tooth Abnormalities/genetics*
  • Tooth Abnormalities/pathology
  • Zebrafish
PubMed: 29348693 Full text @ Eur. J. Hum. Genet.
Blepharocheilodontic syndrome (BCDS) consists of lagophthalmia, ectropion of the lower eyelids, distichiasis, euryblepharon, cleft lip/palate and dental anomalies and has autosomal dominant inheritance with variable expression. We identified heterozygous variants in two genes of the cadherin-catenin complex, CDH1, encoding E-cadherin, and CTNND1, encoding p120 catenin delta1 in 15 of 17 BCDS index patients, as was recently described in a different publication. CDH1 plays an essential role in epithelial cell adherence; CTNND1 binds to CDH1 and controls the stability of the complex. Functional experiments in zebrafish and human cells showed that the CDH1 variants impair the cell adhesion function of the cadherin-catenin complex in a dominant-negative manner. Variants in CDH1 have been linked to familial hereditary diffuse gastric cancer and invasive lobular breast cancer; however, no cases of gastric or breast cancer have been reported in our BCDS cases. Functional experiments reported here indicated the BCDS variants comprise a distinct class of CDH1 variants. Altogether, we identified the genetic cause of BCDS enabling DNA diagnostics and counseling, in addition we describe a novel class of dominant negative CDH1 variants.