Clinical and molecular characterization of Rubinstein‐Taybi syndrome patients carrying distinct novel mutations of the EP300 gene. (17th February 2014)

• Record Type: Journal Article
• Authors: Negri, G.; Milani, D.; Colapietro, P.; Forzano, F.; Della Monica, M.; Rusconi, D.; Consonni, L.; Caffi, L. G.; Finelli, P.; Scarano, G.; Magnani, C.; Selicorni, A.; Spena, S.; Larizza, L.; Gervasini, C.
• Is Part Of: Clinical genetics. Volume 87:Number 2(2015:Feb.)
• Page Start: 148
• Page End: 154
• Publication Date: 2014-02-17
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12348
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12348-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12348-para-0001">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, <italic>CREBBP</italic> and <italic>EP300</italic>, encoding two homologous transcriptional co‐activators, have been identified in ˜55% and ˜3–5% of affected individuals, respectively. To date, only eight <italic>EP300</italic>‐mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, <italic>EP300</italic> analysis was performed on 33 <italic>CREBBP</italic>‐negative RSTS patients leading to the identification of six unreported germline <italic>EP300</italic> 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‐<italic>EP300</italic>‐mutated cohort, this study indicates that <italic>EP300</italic>‐related RSTS cases occur more frequently than previously thought (˜8% <italic>vs</italic> 3–5%); furthermore, the characterization of novel <italic>EP300</italic> mutations in RSTS patients will enhance the clinical practice and genotype–phenotype correlations.</p> </abstract>