Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ~55% and ~3-5% of affected individuals, respectively. To date, only eight EP300-mutated-RSTS patients have been described and twelve additional mutations reported in the LOVD database. In this study, EP300 analysis were performed on 33 CREBBP-negative-RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, our study indicates that EP300-related-RSTS cases occur more frequently than previously thought (~8% vs 3-5%); furthermore novel EP300 mutations characterization in RSTS patients will enhance clinical practice and genotype-phenotype correlations.
Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene / G. Negri, D. Milani, P. Colapietro, F. Forzano, M. Della Monica, D. Rusconi, L. Consonni, L.G. Caffi, P. Finelli, G. Scarano, C. Magnani, A. Selicorni, S. Spena, L. Larizza, C. Gervasini. - In: CLINICAL GENETICS. - ISSN 0009-9163. - 87:2(2015), pp. 148-154.
|Titolo:||Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene|
NEGRI, GLORIA (Primo)
MILANI, DONATELLA (Secondo)
LARIZZA, LIDIA (Corresponding)
|Parole Chiave:||EP300; exonic deletions; genotype-phenotype correlations; point mutations; Rubinstein-Taybi syndrome|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
|Data di pubblicazione:||2015|
|Data ahead of print / Data di stampa:||17-feb-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/cge.12348|
|Appare nelle tipologie:||01 - Articolo su periodico|