TY - JOUR T1 - Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire. JF - Hum Genet Y1 - 2015 A1 - Rusconi, Daniela A1 - Negri, Gloria A1 - Colapietro, Patrizia A1 - Picinelli, Chiara A1 - Milani, Donatella A1 - Spena, Silvia A1 - Magnani, Cinzia A1 - Silengo, Margherita Cirillo A1 - Sorasio, Lorena A1 - Curtisova, Vaclava A1 - Cavaliere, Maria Luigia A1 - Prontera, Paolo A1 - Stangoni, Gabriela A1 - Ferrero, Giovanni Battista A1 - Biamino, Elisa A1 - Fischetto, Rita A1 - Piccione, Maria A1 - Gasparini, Paolo A1 - Salviati, Leonardo A1 - Selicorni, Angelo A1 - Finelli, Palma A1 - Larizza, Lidia A1 - Gervasini, Cristina KW - Adolescent KW - Adult KW - Base Sequence KW - Child KW - Child, Preschool KW - Cohort Studies KW - CREB-Binding Protein KW - Female KW - Humans KW - Infant KW - Infant, Newborn KW - Male KW - Middle Aged KW - Point Mutation KW - Rubinstein-Taybi Syndrome KW - Sequence Deletion AB -

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.

VL - 134 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25805166?dopt=Abstract ER -