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.

Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene

G. Negri
Primo
;
D. Milani
Secondo
;
P. Colapietro;D. Rusconi;P. Finelli;S. Spena;L. Larizza
;
C. Gervasini
Ultimo
2015

Abstract

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.
EP300; exonic deletions; genotype-phenotype correlations; point mutations; Rubinstein-Taybi syndrome
Settore MED/03 - Genetica Medica
17-feb-2014
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/233787
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