PUBLICATION
Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome
- Authors
- 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.
- ID
- ZDB-PUB-180120-6
- 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.
Citation
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. (2018) Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome. European journal of human genetics : EJHG. 26(2):210-219.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping