Mutations in transcription factor p63 are associated with developmental disorders that manifest defects in stratified epithelia including the epidermis.
p53 and p63 share extensive sequence and structure homology. p53 is frequently mutated in cancer, whereas mutations in p63 cause developmental disorders manifested in ectodermal dysplasia, limb defects, and orofacial clefting.
EEC (ectrodactyly, ectodermal dysplasia, clefting; OMIM 604292) is an autosomal dominant developmental disorder resulting mainly from pathogenic mutations of the DNA-binding domain (DBD) of the TP63 gene.
Causative TP63 mutations have been identified in five distinct human developmental disorders that are characterized by various degrees of limb abnormalities, ectodermal dysplasia, and facial clefts.