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.

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. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 155(12), 3104-3109 [10.1002/ajmg.a.34335].

Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes

MELINO, GENNARO;Terrinoni, A.
2011

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/12
English
Amino Acid Sequence; Anodontia; Base Sequence; Breast; Cell Line; Cleft Lip; Cleft Palate; Ectodermal Dysplasia; Eye Abnormalities; Eyelids; HEK293 Cells; Humans; Infant; Lacrimal Duct Obstruction; Limb Deformities, Congenital; Male; Nails, Malformed; Pigmentation Disorders; Transcription Factors; Tumor Suppressor Proteins; Mutation; Phenotype
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. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 155(12), 3104-3109 [10.1002/ajmg.a.34335].
Serra, V; Castori, M; Paradisi, M; Bui, L; Melino, G; Terrinoni, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/131489
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