Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP

  title={Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP},
  author={Fred Petrif and Rachel H. Giles and Hans G. Dauwerse and Jasper J. Saris and Raoul C.M. Hennekam and Mitsuo Masuno and Niels Tommerup and Gert-Jan B. van Ommen and Richard H. Goodman and Dorien J. M. Peters and Martijn H. Breuning},
THE Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features1-3. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16pl3.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-A IMP… 

Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations

Diagnostic analysis of CBP is reported in 194 RTS patients, divided into several subsets, in one case the mother is also suspect of having RTS, and two point mutations, one 11 bp deletion, and one mutation affecting the splicing of the second exon were detected by subsequent sequencing.

Rubinstein-Taybi Syndrome and Epigenetic Alterations.

  • E. Korzus
  • Biology
    Advances in experimental medicine and biology
  • 2017
A role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus, but it is difficult to establish a direct role forCBP in cognitive function in the adult brain.

Diagnostic analysis of th Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations Petrij,

Diagnosis of CBP is reported in 194 RTS patients, divided into several subsets, in one case the mother is also suspect of having RTS, and analyses of the entire CBP gene by the protein truncation test showed 4/37 truncating mutations.

Analysis of CBP (CREBBP) gene deletions in Rubinstein‐Taybi syndrome patients using real‐time quantitative PCR

The results suggest that real‐time quantitative PCR is a useful technique to be included in the deletion search in RTS patients and identify deletions at the 3′ end of the gene that had been missed by FISH analysis, and to refine some deletion breakpoints.

Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome

Different molecular techniques are reported here the use of to analyse the CBP gene in a cohort of 60 RTS patients, using cDNA probes to search for gross rearrangements by Southern blot analysis and to identify CBP mRNA of abnormal sizes on northern blots, intragenic microsatellite markers to look for intragenics deletions, as well as a complete series of primers to PCR amplify each of the 31 exons of the gene for mutation searching by direct sequencing.

Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients

A high detection rate (61.3%) of mutations is confirmed by this Italian study which also attests one of the highest microdeletion rate (16%) documented so far.

Rubinstein-Taybi syndrome caused by a De Novo reciprocal translocation t(2;16)(q36.3;p13.3).

The results suggest that the loss of C-terminal domains of CBP is sufficient to cause Rubinstein-Taybi syndrome, and indicate the potential utility of Western blot analysis as an inexpensive and fast approach for screening RTS mutations.

Rubinstein–Taybi syndrome: clinical and molecular overview

The clinical presentation of Rubinstein–Taybi syndrome is described, the mutation spectrum is reviewed, and the current understanding of causative molecular mechanisms is discussed.

A case of Rubinstein-Taybi Syndrome with a CREB-binding protein gene mutation

A typical RTS patient with Arnold-Chiari malformation, identified by mutational analysis, has a mutation in the CREBBP gene, c.4944_4945insC, which is understood to be associated with cell growth and proliferation.

Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.

There is a direct link between loss of acetyl transferase activity and RSTS, which indicates that the disorder is caused by aberrant chromatin regulation and the search for mutations to the EP300 gene was extended and showed that mutations in EP300 also cause this disorder.



Rubinstein-Taybi syndrome caused by submicroscopic deletions within 16p13.3.

By using two-color fluorescence in situ hybridization, the signal from RT1 was found to be missing from one chromosome 16 in 6 of 24 patients with RTS, and the parents of five patients did not show a deletion of RT1, indicating a de novo rearrangement.

Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene

It is shown that some families with WS have mutations in the human homologue9 of Pax-3, which is one of a family of eight Pax genes known in mice which are involved in regulating embryonic development and which contains a highly conserved transcription control sequence, the paired box.

Confirmation of assignment of a locus for Rubinstein-Taybi syndrome gene to 16p13.3.

Ch Chromosome analysis demonstrated a de novo pericentric inversion of one chromosome 16: 46,XX,inv(16)(p13.3;q13).

Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2

A further three PAX3 mutations are described which cause Waardenburg syndrome; one alters the octapeptide motif plus the presumed homeodomain; a second alters all three elements and the third alters the paired box alone.

Mutations in the paired domain of the human PAX3 gene cause Klein-Waardenburg syndrome (WS-III) as well as Waardenburg syndrome type I (WS-I).

The results indicate that mutations in the PAX3 gene can cause both WS-I and WS-III, and two new mutations are described that are associated with WS.

Rubinstein-Taybi syndrome with de novo reciprocal translocation t(2;16)(p13.3;p13.3).

Cytogenetic studies of a girl with typical Rubinstein-Taybi syndrome with apparently balanced reciprocal translocation between chromosome 2 and 16 suggest that the locus of the gene for the Rubenstein-T Taybi syndrome may be situated at 2p13.3 or 16p 13.3.

Tentative assignment of a locus for Rubinstein-Taybi syndrome to 16p13.3 by a de novo reciprocal translocation, t(7;16)(q34;p13.3).

During a systematic chromosomal survey of 7 unrelated patients with Rubinstein-Taybi syndrome, an apparently balanced de novo reciprocal translocation, t(7;16)(q34;p 13.3), was detected in an affected boy, suggesting that a locus for this syndrome maps to 16p13.3.

Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma

The PAX3 gene alterations are associated with two completely unrelated human diseases, paediatric solid tumour alveolar rhabdomyosarcoma and Leigh's syndrome.

Submicroscopic deletion of chromosome region 16p13.3 in a Japanese patient with Rubinstein-Taybi syndrome.

In a series of 25 Japanese patients with Rubinstein-Taybi syndrome, we screened, by high-resolution GTG banding and fluorescence in situ hybridization of a cosmid probe (RT1, D16S237), for