Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate (EEC) Syndrome Study

Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Heterozygous mutations of TP63 encoding p63 cause a spectrum of developmental disorders. EEC syndrome is caused by point mutations in the p63 DNA-binding domain, and manifests ectodermal dysplasia with defects in the epidermis and epidermal related appendages, limb malformation and cleft lip/palate. Five hotspot mutations affecting amino acids, R204, R227, R279, R280 and R304, have been found in approximately 90% of the EEC population. Although the role of p63 in normal epidermal development and differentiation has been demonstrated, the molecular mechanism by which p63 mutations cause the epidermal phenotype in diseases is not yet understood. In the two related studies, we characterize p63 mutant keratinocytes (R204W, R279H and R304W) and p63 mutant iPSCs (R204W and R304W) and the molecular mechanisms underlying their differentiation defects.]]>
Clinical InformationBarcode InformationPrimary keratinocytes were established previously from skin biopsies of three EEC syndrome patients carrying heterozygous mutations in the p63 DNA-binding domain, R204W, R279H, and R304W. These three patients have been included in the studies which showed p63 mutations are the cause of EEC syndrome. iPSCs were generated from fibroblasts of two EEC syndrome patients carrying R204W and R304W mutations, by introducing Oct4, Sox2, Klf4 and cMyc genes via lentiviral transduction.]]>