Two Novel TP63 Mutations Associated With the Ankyloblepharon, Ectodermal Defects, and Cleft Lip and Palate Syndrome

Payne, Aimee; Yan, Albert C.; Ilyas, Erum; Li, Weijie; Seykora, John T.; Young, Terri L.; Pawel, Bruce; Honig, Paul J.; Camacho, Jeanette; Imaizumi, Sonia; Heymann, Warren R.; Schnur, Rhonda E.

doi:10.1001/archderm.141.12.1567

Cited by 40 publications

(37 citation statements)

References 40 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the absence of Perp expression, mice display severe intra-epidermal blistering further underscoring the importance of Perp in cell adhesion. Consistent with these findings, cell adhesion defects have also been reported in AEC patients, a subset of who display aberrant Perp expression (Payne et al , 2005;Beaudry et al , 2009). …”

Section: P63 In Epidermal Development and Maintenancesupporting

confidence: 71%

p63 in Skin Development and Ectodermal Dysplasias

Koster

2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

The transcription factor p63 is critically important for skin development and maintenance. Processes that require p63 include epidermal lineage commitment, epidermal differentiation, cell adhesion, and basement membrane formation. Not surprisingly, alterations in the p63 pathway underlie a subset of ectodermal dysplasias, developmental syndromes in which the skin and skin appendages do not develop normally. This review summarizes the current understanding of the role of p63 in normal development and ectodermal dysplasias.

show abstract

Section: P63 In Epidermal Development and Maintenancesupporting

confidence: 71%

p63 in Skin Development and Ectodermal Dysplasias

Koster

2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Global gene expression analysis comparing a relatively large number of samples of skin from AEC patients versus normal controls demonstrated a reduced expression of FRAS1 and COL7A1 in AEC skin, which was confirmed by quantitative RT-PCR and immunostaining (Clements et al 2012). In a case report, induction of mechanical stress in a skin biopsy consistently caused cytolysis and focal disruption of anchoring fibrils at electron microscopy (Payne et al 2005).…”

Section: P63 Regulation Of Cell-matrix Adhesionmentioning

confidence: 94%

“…Similarly to AEC syndrome, desmosomal diseases such as P. vulgaris and P. foliaceus are commonly more severe on the scalp, which has been considered as a consequence of the regional expression of desmosomal proteins (Ioannides et al 1991). Consistent with a disruption in desmosomal components, intra-epidermal blistering with areas of both acantholysis and cytolysis was reported in perilesional skin of a newborn AEC patient after mechanical rubbing (Payne et al 2005). In further support of possible desmosome involvement in AEC syndrome, adult patients can be affected by palmoplantar hyperkeratosis and erosive palmoplantar keratoderma with bleeding after extensive walking, a typical feature of desmosomal gene dysfunction.…”

Section: P63 and Desmosomesmentioning

confidence: 99%

Epidermal cell junctions and their regulation by p63 in health and disease

2015

View full text Add to dashboard Cite

As the outermost tissue of the body, the epidermis is the first physical barrier for any pressure, stress or trauma. Several specialized cell-matrix and cell-cell adhesion structures, together with an intracellular network of dedicated intermediate filaments, are required to confer critical resilience to mechanical stress. The transcription factor p63 is a master regulator of gene expression in the epidermis and in other stratified epithelia. It has been extensively demonstrated that p63 positively controls a large number of tissue-specific genes, including those encoding a large fraction of tissue-restricted cell adhesion molecules. Consistent with p63 functions in cell adhesion and in epidermal differentiation, heterozygous mutations clustered mainly in the p63 C-terminus are causative of AEC syndrome, an autosomal dominant disorder characterized by cleft palate, ankyloblepharon and ectodermal dysplasia associated with severe skin erosions, bleeding and infections. The molecular basis of skin erosions in AEC patients is not fully understood, although defects in desmosomes and in other cell junctions are likely to be involved. Here, we provide an extensive review of the different epidermal cell junctions that cooperate to withstand mechanical stress and on the mechanisms by which p63 regulates gene expression of their components in healthy skin and in AEC syndrome. Collectively, advancement in understanding the molecular mechanisms by which epidermal cell junctions precisely exert their functions and how p63 orchestrates their coordinated expression, will ultimately lead to insight into developing future strategies for the treatment of AEC syndrome and more in generally for diseases that share an overlapping phenotype.

show abstract

“…They are either point mutations in the SAM domain or deletions in the SAM or TI domains (Table 1). 7,11,12,[24][25][26][27][28][29][30][31][32][33][34][35] The SAM domain is known to be involved in protein-protein interactions and therefore mutations in this domain are most probably hampering the binding to interacting proteins. One known interactor of p63 SAM domain is the Apobec-1-binding protein-1 (ABBP1), which is a member of RNA processing machinery and known to regulate the alternative splicing of the Fibroblast-growth-factor-receptor-2 (FGFR2) towards the epithelial specific isoform.…”

Section: Allelic P63 Conditionsmentioning

confidence: 99%

p63-Associated Disorders

Brunner²,

2007

View full text Add to dashboard Cite

AcKnowledGemenTsWe thank Ben Hamel, Hans Scheffer and Rowdy Meijer in clinical and diagnostic investigations, and all p63 syndrome patients and clinicians all over the world, who have made this study feasible. Work in our laboratory is supported by European Union Sixth Framework programme EpiStem project (LSHB-CT-2005-019067). ABsTRAcTHeterozygous mutations in the transcription factor gene p63 are causative for several syndromes with ectodermal dysplasia, orofacial clefting and limb malformations as the key characteristics. Different combinations of these features are seen in five different syndromes, of which ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC) is the most common one. Mutations in p63 can also cause non-syndromic single malformations, such as split hand foot malformation (SHFM4) and isolated cleft lip (NSCL). In this article we will present an overview of diseases caused by mutations in the p63 gene and review the known pathogenic p63 gene mutations.

show abstract

Two Novel TP63 Mutations Associated With the Ankyloblepharon, Ectodermal Defects, and Cleft Lip and Palate Syndrome

Cited by 40 publications

References 40 publications

p63 in Skin Development and Ectodermal Dysplasias

p63 in Skin Development and Ectodermal Dysplasias

Epidermal cell junctions and their regulation by p63 in health and disease

p63-Associated Disorders

Contact Info

Product

Resources

About