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

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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


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
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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