title: Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes.
abstract: 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.
authors: IDI-IRCCS Biochemistry Laboratory, c/o Department of Experimental Medicine, University of Tor Vergata, Rome, Italy.
authors: Valeria
authors: V
authors: Serra
authors: Marco
authors: M
authors: Castori
authors: Mauro
authors: M
authors: Paradisi
authors: Laura
authors: L
authors: Bui
authors: Gerry
authors: G
authors: Melino
authors: Alessandro
authors: A
authors: Terrinoni
mesh_terms: D000595:Amino Acid Sequence; D000848:Anodontia / Q000175:diagnosis / Q000235:genetics*; D001483:Base Sequence; D001940:Breast / Q000002:abnormalities; D002460:Cell Line; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005124:Eye Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005143:Eyelids / Q000002:abnormalities; D057809:HEK293 Cells; D006801:Humans; D007223:Infant; D007767:Lacrimal Duct Obstruction / Q000175:diagnosis / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D009264:Nails, Malformed / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D010859:Pigmentation Disorders / Q000175:diagnosis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins