<unk>  is autosomal dominant, caused by a missense mutation in the Sterile alpha motif (SAM) of the TP73L (p63) gene which encodes for a protein-protein interaction domain. It is a very rare disorder.<unk>  is an autosomal dominant pattern of inheritance. The syndrome is thought to arise from a missense mutation in a gene pivotal for the proper development of craniofacial structures and extremities, as well as skin differentiation. Specifically, mutations within the Tumor Protein 63 gene have been implicated in<unk> . Residing on the long-arm of chromosome 3, the Tumor Protein 63 (TP63) gene is critical for proper development and homeostasis of stratified epithelia. In<unk> , and other ectodermal dysplasia disorders, a missense, nonsense, or insertion mutation has occurred in the TP63 gene. Currently, no deletion or duplication mutations have been detected in such disorders. Although ectodermal dysplasia disorders result from heterozygous mutations in TP63, compromised epidermal differentiation with epidermal decay is representative of<unk> -Wells patients but is hardly observed in other syndromes. In contrast, severe abnormalities characteristic of other ectodermal dysplasia disorders (i.e. limb abnormalities in EEC) are not seen in<unk> -Wells patients. Proteomics TP63 encodes for the p63 transcription factor, which is implicated in proliferation, differentiation, apoptosis, regular cell maintenance, and cell adhesion. Specifically, p63 is expressed within early keratinocytes and the embryonic ectodermal ridge during development. Thus, p63 is believed to play a pivotal role in the development and maintenance of the epidermis. Reported mutations that have resulted in<unk>  have occurred within the sterile alpha motif (SAM) and the transactivation inhibitory (TI) domains of the p63-coding region. The SAM domain of p63 is thought to be imperative for protein-protein interactions, while the TI domain may play a role in the repression of other isoforms of p63. Recent work has shown that mutations within these domains lead to repression of other known transcriptional activators of epidermal differentiation. These transcription activators include: GRHL3, HOPX, PRDM1, KLF4, and ZNF750. Most notably,<unk> -Wells-type p63 mutations cause irregular repression of the genes that encode for ZNF750. The down-regulation of ZNF750 has been shown to hinder the expression of the other before mentioned differentiation-activators such as HOPX, PRDM1, KLF4, and GRHL3. In contrast, recapitulating the expression of ZNF750 leads to significant rescue of normal epidermal differentiation. Phenotype<unk>  is the result of the invariant mutations of the p63 transcription factor that have been previously identified. Due to the diminished activities of p63, patients can experience a host of symptoms related to the operation of keratinocytes. In particular, the hypopigmentation observed in several<unk> -Wells patients is believed to be the result of improperly developed keratinocytes not being able to properly interact with melanocytes. However, as it stands, this display of<unk>  has not been entirely comprehended. Most noted are the abnormal development of hair, teeth, glands, and nails.
Hay–Wells syndrome
Kindler syndrome
Hurler syndrome
Birk-Barel syndrome
Baboon syndrome
Muckle–Wells syndrome
Hecht Scott syndrome
GRACILE syndrome