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Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype.

Publication ,  Journal Article
Payne, AS; Yan, AC; Ilyas, E; Li, W; Seykora, JT; Young, TL; Pawel, BR; Honig, PJ; Camacho, J; Imaizumi, S; Heymann, WR; Schnur, RE
Published in: Arch Dermatol
December 2005

BACKGROUND: Ankyloblepharon, ectodermal defects, and cleft lip and palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the sterile alpha motif region of TP63, a homologue of the tumor suppressor TP53. Recent structure-function studies have identified complexities in the genotype-phenotype correlation of the p63 syndromes. OBSERVATIONS: We report 2 sporadic cases of AEC syndrome in infants. Both patients demonstrated skin erosions with prominent scalp involvement. Histologic studies demonstrated mild basal layer vacuolization and rare dyskeratotic keratinocytes, with evidence of both acantholysis and cytolysis at the blister edge. Immunohistochemistry using anti-p63 monoclonal antibody demonstrated basal epidermal nuclear staining in both healthy control and patient tissue samples. Ultrastructural studies showed focal disruption of anchoring fibrils near the blister edge of one patient and normal desmosomes, hemidesmosomes, and basement membrane zone in the nonblistered skin of the other patient. The DNA analysis of each patient revealed 2 novel missense mutations in the TP63 gene that resulted in L514S and R555P amino acid substitutions within the sterile alpha motif region of the p63 protein. CONCLUSIONS: We report 2 novel TP63 mutations resulting in AEC syndrome. The R555P mutation is the most carboxy-terminal of all the reported AEC missense mutations of p63. The presence of skin fragility, manifested as erosive skin lesions in body areas in addition to the scalp, is postulated to be an important diagnostic feature of AEC syndrome.

Duke Scholars

Published In

Arch Dermatol

DOI

ISSN

0003-987X

Publication Date

December 2005

Volume

141

Issue

12

Start / End Page

1567 / 1573

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Transcription Factors
  • Trans-Activators
  • Syndrome
  • Skin
  • Proline
  • Phosphoproteins
  • Phenotype
  • Mutation, Missense
  • Male
 

Citation

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Payne, A. S., Yan, A. C., Ilyas, E., Li, W., Seykora, J. T., Young, T. L., … Schnur, R. E. (2005). Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. Arch Dermatol, 141(12), 1567–1573. https://doi.org/10.1001/archderm.141.12.1567
Payne, Aimee S., Albert C. Yan, Erum Ilyas, Weijie Li, John T. Seykora, Terri L. Young, Bruce R. Pawel, et al. “Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype.Arch Dermatol 141, no. 12 (December 2005): 1567–73. https://doi.org/10.1001/archderm.141.12.1567.
Payne AS, Yan AC, Ilyas E, Li W, Seykora JT, Young TL, et al. Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. Arch Dermatol. 2005 Dec;141(12):1567–73.
Payne, Aimee S., et al. “Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype.Arch Dermatol, vol. 141, no. 12, Dec. 2005, pp. 1567–73. Pubmed, doi:10.1001/archderm.141.12.1567.
Payne AS, Yan AC, Ilyas E, Li W, Seykora JT, Young TL, Pawel BR, Honig PJ, Camacho J, Imaizumi S, Heymann WR, Schnur RE. Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. Arch Dermatol. 2005 Dec;141(12):1567–1573.

Published In

Arch Dermatol

DOI

ISSN

0003-987X

Publication Date

December 2005

Volume

141

Issue

12

Start / End Page

1567 / 1573

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Transcription Factors
  • Trans-Activators
  • Syndrome
  • Skin
  • Proline
  • Phosphoproteins
  • Phenotype
  • Mutation, Missense
  • Male