The Rapp–Hodgkin syndrome results from mutations of the TP63 gene

Gaëlle Bougeard (1) , Smail Hadj-Rabia (2) , Laurence Faivre (3) , Nasrin Sarafan-Vasseur (1) , Thierry Frebourg (1)

1 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
2 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement
3 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)

The Rapp-Hodgkin syndrome (RHS, MIM 129400) corresponds to a rare form of anhydrotic ectodermal dysplasia, which shares some features with the ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome (EEC, MIM 604292) resulting from TP63 mutations. We report here, in two unrelated patients with RHS, the identification of two distinct TP63 mutations, corresponding to a novel frameshift mutation (1709DelA, exon 14) located downstream the sterile alpha motif (SAM) domain and to a missense mutation (R279H, exon 7) within the DNA binding domain. Functional analysis of the R279H mutation, which had previously been reported in several EEC families, shows that this mutation disrupted the dominant negative activity of the DeltaNp63alpha and gamma isoforms on the transcriptional activity of TP53. This report shows, on a molecular basis, that RHS is also an EEC-like syndrome resulting from mutations of the TP63 gene, and highlights the wide phenotypic spectrum associated to TP63 mutations.

Domaines: Génétique humaine

Gaëlle Bougeard, Smail Hadj-Rabia, Laurence Faivre, Nasrin Sarafan-Vasseur, Thierry Frebourg. The Rapp–Hodgkin syndrome results from mutations of the TP63 gene. European Journal of Human Genetics, 2003, 11 (9), pp.700-704. ⟨10.1038/sj.ejhg.5201004⟩. ⟨hal-03106944⟩