Publication Type:

Journal Article

Source:

Eur J Hum Genet, Volume 26, Issue 2, p.210-219 (2018)

Abstract:

<p>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.</p>

Cite this Research Publication

A. Kievit, 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., Lopes, V. L. Gil-da S., Lustosa-Mendes, E., Krall, M., Slavotinek, A., Martinez-Glez, V., Bakkers, J., van Gassen, K. L. I., de Klein, A., van den Boogaard, M. - J. H., and van Haaften, G., “Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome.”, Eur J Hum Genet, vol. 26, no. 2, pp. 210-219, 2018.

207
PROGRAMS
OFFERED
5
AMRITA
CAMPUSES
15
CONSTITUENT
SCHOOLS
A
GRADE BY
NAAC, MHRD
8th
RANK(INDIA):
NIRF 2018
150+
INTERNATIONAL
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