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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.AD

Abstract

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.

Authors+Show Affiliations

Department of Dermatology, University of Pennsylvania, 220 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA. aimee.payne@uphs.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

16365259

Citation

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." Archives of Dermatology, vol. 141, no. 12, 2005, pp. 1567-73.
Payne AS, Yan AC, Ilyas E, 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;141(12):1567-73.
Payne, A. S., Yan, A. C., Ilyas, E., Li, W., Seykora, J. T., Young, T. L., Pawel, B. R., Honig, P. J., Camacho, J., Imaizumi, S., Heymann, W. R., & Schnur, R. E. (2005). Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. Archives of Dermatology, 141(12), 1567-73.
Payne AS, 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;141(12):1567-73. PubMed PMID: 16365259.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two novel TP63 mutations associated with the ankyloblepharon, ectodermal defects, and cleft lip and palate syndrome: a skin fragility phenotype. AU - Payne,Aimee S, AU - Yan,Albert C, AU - Ilyas,Erum, AU - Li,Weijie, AU - Seykora,John T, AU - Young,Terri L, AU - Pawel,Bruce R, AU - Honig,Paul J, AU - Camacho,Jeanette, AU - Imaizumi,Sonia, AU - Heymann,Warren R, AU - Schnur,Rhonda E, PY - 2005/12/21/pubmed PY - 2006/2/24/medline PY - 2005/12/21/entrez SP - 1567 EP - 73 JF - Archives of dermatology JO - Arch Dermatol VL - 141 IS - 12 N2 - 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. SN - 0003-987X UR - https://www.unboundmedicine.com/medline/citation/16365259/Two_novel_TP63_mutations_associated_with_the_ankyloblepharon_ectodermal_defects_and_cleft_lip_and_palate_syndrome:_a_skin_fragility_phenotype_ L2 - https://jamanetwork.com/journals/jamadermatology/fullarticle/10.1001/archderm.141.12.1567 DB - PRIME DP - Unbound Medicine ER -