Getting under the skin of p63.
Mutations in the transcription factor gene p63 are causative for human developmental syndromes characterized by three main hallmarks: ectodermal dysplasia, limb malformations and orofacial clefting. Five different dominantly inherited human syndromes and two non-syndromic conditions have been linked to p63 gene defects. Ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC) is the most common p63-associated condition, since approximately 60 percent of all p63 mutations have been identified in EEC syndrome patients. Other p63-linked syndromes: AEC, LMS, ADULT and RHS, all show overlapping features of the three main disease characteristics. In contrast, isolated split hand/foot malformation (SHFM4) and non-syndromic cleft lip/palate (NSCL) only show one of the three main hallmarks. In this study I have tried to get more insight into the p63-associated diseases, their molecular disease mechanism and the role of p63 and its downstream signaling in these diseases.