How to cite this article: Rinne T, Bolat E, Meijer R, Scheffer H, van Bokhoven H. 2009. Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). Am J Med Genet Part A 149A:1948–1951.
Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC)†
Article first published online: 12 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Special Issue: Ankyloblepharon-Ectodermal Defects-Cleft Lip and/or Palate Syndrome and Ectodermal Dysplasias
Volume 149A, Issue 9, pages 1948–1951, September 2009
How to Cite
Rinne, T., Bolat, E., Meijer, R., Scheffer, H. and van Bokhoven, H. (2009), Spectrum of p63 mutations in a selected patient cohort affected with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). Am. J. Med. Genet., 149A: 1948–1951. doi: 10.1002/ajmg.a.32793
- Issue published online: 20 AUG 2009
- Article first published online: 12 AUG 2009
- Manuscript Accepted: 4 FEB 2009
- Manuscript Received: 24 AUG 2008
- National Foundation for Ectodermal Dysplasias
- European Union Sixth Framework program EpiStem project. Grant Number: LSHB-CT-2005-019067
- ectodermal dysplasia;
Heterozygous mutations in the p63 gene underlie a group of at least seven allelic syndromes, including ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC) and Rapp Hodgkin syndrome (RHS), which involves varying degrees of ectodermal dysplasia, orofacial clefting and limb malformations. Mutations in the AEC and Rapp Hodgkin syndromes cluster in the 3′ end of the p63 gene. Previously reported mutations are mainly missense and frameshift mutations in exons 13 and 14, affecting the p63α-specific SAM (sterile alpha motif) and TI (transactivation inhibitory) domains. A patient cohort affected by AEC syndrome was evaluated during International Research Symposium supported by the National Foundation for Ectodermal Dysplasias. Nineteen patients underwent full clinical evaluations and 18 had findings consistent with a diagnosis of AEC syndrome. These 19 patients, along with 5 additional relatives had genomic DNA analysis. Twenty-one of the 24 participants from 12 families were found to have mutations in the p63 gene. Eleven different mutations were identified; 10 were novel mutations. Eight were missense mutations within the coding region of the SAM domain. Three other mutations were located in exon 14 sequences, which encode the TI domain. The effects of the mutations in the SAM and TI domains are poorly understood and functional studies are required to understand the pathological mechanisms. However, AEC and RHS mutations in the 5′ and 3′ ends of the p63 gene point towards a critical role of the ΔNp63α isoform for the AEC/RHS phenotype. © 2009 Wiley-Liss, Inc.