Media type: E-Article Title: Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp‐Hodgkin/AEC/ADULT syndromes Contributor: Serra, Valeria; Castori, Marco; Paradisi, Mauro; Bui, Laura; Melino, Gerry; Terrinoni, Alessandro Published: Wiley, 2011 Published in: American Journal of Medical Genetics Part A, 155 (2011) 12, Seite 3104-3109 Language: English DOI: 10.1002/ajmg.a.34335 ISSN: 1552-4825; 1552-4833 Origination: Footnote: Description: AbstractHeterozygous 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.