TY - JOUR
T1 - Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome /692/699 /631/208/1516 article
AU - Kievit, Anneke
AU - Tessadori, Federico
AU - Douben, Hannie
AU - Jordens, Ingrid
AU - Maurice, Madelon
AU - Hoogeboom, Jeannette
AU - Hennekam, Raoul
AU - Nampoothiri, Sheela
AU - Kayserili, H. lya
AU - Castori, Marco
AU - Whiteford, Margo
AU - Motter, Connie
AU - Melver, Catherine
AU - Cunningham, Michael
AU - Hing, Anne
AU - Kokitsu-Nakata, Nancy M.
AU - Vendramini-Pittoli, Siulan
AU - Richieri-Costa, Antonio
AU - Baas, Annette F.
AU - Breugem, Corstiaan C.
AU - Duran, Karen
AU - Massink, Maarten
AU - Derksen, Patrick W. B.
AU - van Ijcken, Wilfred F. J.
AU - van Unen, Leontine
AU - Santos-Simarro, Fernando
AU - Lapunzina, Pablo
AU - Gil-da Silva Lopes, Vera L.
AU - Lustosa-Mendes, Elaine
AU - Krall, Max
AU - Slavotinek, Anne
AU - Martinez-Glez, Victor
AU - Bakkers, Jeroen
AU - van Gassen, Koen L. I.
AU - de Klein, Annelies
AU - van den Boogaard, Marie-José H.
AU - van Haaften, Gijs
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85040706144&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29348693
U2 - 10.1038/s41431-017-0010-5
DO - 10.1038/s41431-017-0010-5
M3 - Article
C2 - 29348693
VL - 26
SP - 210
EP - 219
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -