Characterization of 14 novel deletions underlying Rubinstein–Taybi syndrome: an update of the CREBBP deletion repertoire

Daniela Rusconi, Gloria Negri, Patrizia Colapietro, Chiara Picinelli, Donatella Milani, Silvia Spena, Cinzia Magnani, Margherita Cirillo Silengo, Lorena Sorasio, Vaclava Curtisova, Maria Luigia Cavaliere, Paolo Prontera, Gabriela Stangoni, Giovanni Battista Ferrero, Elisa Biamino, Rita Fischetto, Maria Piccione, Paolo Gasparini, Leonardo Salviati, Angelo SelicorniPalma Finelli, Lidia Larizza, Cristina Gervasini

Research output: Contribution to journalArticlepeer-review


Rubinstein–Taybi syndrome (RSTS) is a rare, clinically heterogeneous disorder characterized by cognitive impairment and several multiple congenital anomalies. The syndrome is caused by almost private point mutations in the CREBBP (~55 % of cases) and EP300 (~8 %) genes. The CREBBP mutational spectrum is variegated and characterized by point mutations (30–50 %) and deletions (~10 %). The latter are diverse in size and genomic position and remove either the whole CREBBP gene and its flanking regions or only an intragenic portion. Here, we report 14 novel CREBBP deletions ranging from single exons to the whole gene and flanking regions which were identified by applying complementary cytomolecular techniques: fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and array comparative genome hybridization, to a large cohort of RSTS patients. Deletions involving CREBBP account for 23 % of our detected CREBBP mutations, making an important contribution to the mutational spectrum. Genotype–phenotype correlations revealed that patients with CREBBP deletions extending beyond this gene did not always have a more severe phenotype than patients harboring CREBBP point mutations, suggesting that neighboring genes play only a limited role in the etiopathogenesis of CREBBP-centerd contiguous gene syndrome. Accordingly, the extent of the deletion is not predictive of the severity of the clinical phenotype.

Original languageEnglish
Pages (from-to)613-626
Number of pages14
JournalHuman Genetics
Issue number6
Publication statusPublished - Jun 1 2015

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)


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