How to Cite this Article: Serra V, Castori M, Paradisi M, Bui L, Melino G, Terrinoni A. 2011. Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes. Am J Med Genet Part A 155: 3104–3109.
Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes†
Article first published online: 8 NOV 2011
Copyright © 2011 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 155, Issue 12, pages 3104–3109, December 2011
How to Cite
Serra, V., Castori, M., Paradisi, M., Bui, L., Melino, G. and Terrinoni, A. (2011), Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes. Am. J. Med. Genet., 155: 3104–3109. doi: 10.1002/ajmg.a.34335
- Issue published online: 21 NOV 2011
- Article first published online: 8 NOV 2011
- Manuscript Accepted: 5 SEP 2011
- Manuscript Received: 21 JUL 2011
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- Alleanza contro il Cancro. Grant Number: ACC12-ACC6
- MIUR/PRIN. Grant Number: RBIP06LCA9_0023
- AIRC. Grant Number: 2008–2010_33–08
- Italian Human ProteomeNet. Grant Number: RBRN07BMCT_007
- Telethon. Grant Number: GGPO9133
- Ministero della Salute. Grant Numbers: RF06-RF07, PRIN08
- clinical variability;
- skin erosion
Heterozygous mutations in TP63 cause a wide spectrum of autosomal dominant developmental disorders variably affecting skin, limbs, and face. TP63 encodes p63, a protein expressed in two main isoforms (Tap63 and ΔNp63) with critical roles in both cell differentiation and development. Some analyses suggest a relationship of the mutation site to the observed clinical picture, although this link is inconsistent. This suggests an appreciable phenotypic continuity within the TP63-related disorders. We report a 3-month-old boy ascertained for congenital scalp erosion and mild features of ectodermal dysplasia. His mother showed full-blown characteristics of Rapp-Hodgkin syndrome plus intense abdominal and popliteal freckling. Molecular investigation identified the novel TP63 mutation c.1697delG. We used a luciferase reporter assay to compare the effects on the p63 transactivation (TA) activity of c.1697delG with that of the p.Arg280Cys and p.Gln634X mutations, associated with ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome and isolated split hand/foot malformation, respectively. These results demonstrated complex behavior of c.1697delG in the TA of genes involved in epidermal differentiation and development and shed further light in the physiopathology of TP63-related disorders. © 2011 Wiley Periodicals, Inc.