title: Characterization of 14 novel deletions underlying Rubinstein-Taybi syndrome: an update of the CREBBP deletion repertoire.
abstract: 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.
authors: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Via A. di Rudinì, 8, 20142, Milan, Italy.
authors: Daniela
authors: D
authors: Rusconi
authors: Gloria
authors: G
authors: Negri
authors: Patrizia
authors: P
authors: Colapietro
authors: Chiara
authors: C
authors: Picinelli
authors: Donatella
authors: D
authors: Milani
authors: Silvia
authors: S
authors: Spena
authors: Cinzia
authors: C
authors: Magnani
authors: Margherita Cirillo
authors: MC
authors: Silengo
authors: Lorena
authors: L
authors: Sorasio
authors: Vaclava
authors: V
authors: Curtisova
authors: Maria Luigia
authors: ML
authors: Cavaliere
authors: Paolo
authors: P
authors: Prontera
authors: Gabriela
authors: G
authors: Stangoni
authors: Giovanni Battista
authors: GB
authors: Ferrero
authors: Elisa
authors: E
authors: Biamino
authors: Rita
authors: R
authors: Fischetto
authors: Maria
authors: M
authors: Piccione
authors: Paolo
authors: P
authors: Gasparini
authors: Leonardo
authors: L
authors: Salviati
authors: Angelo
authors: A
authors: Selicorni
authors: Palma
authors: P
authors: Finelli
authors: Lidia
authors: L
authors: Larizza
authors: Cristina
authors: C
authors: Gervasini
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D050882:CREB-Binding Protein / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D050882:CREB-Binding Protein; C494363:CREBBP protein, human