As mutants of p63 in humans exhibit phenotypes that cause several autosomal dominantly inherited syndromes leading to developmental malformations, we tested the transcriptional response of TAp63γ mutants derived from the EEC, SHFM and ADULT syndromes.
These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes.
The expanding p63 mutation database demonstrates that there is overlap between Rapp-Hodgkin syndrome and several other ectodermal dysplasia syndromes, notably Hay-Wells syndrome, and that characterization of the functional consequences of these p63 gene mutations at a molecular and cellular level is likely to provide further insight into the clinical spectrum of these developmental malformation syndromes.
These results confirm that ADULT syndrome is a clinically as well as molecularly distinct member of the expanding p63 mutation family of human malformation syndromes.