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

Fred Petrif; Rachel H. Giles; Hans G. Dauwerse; Jasper J. Saris; Raoul C.M. Hennekam; Mitsuo Masuno; Niels Tommerup; Gert Jan B. van Ommen; Richard H. Goodman; Dorien J.M. Peters; Martijn H. Breuning

doi:10.1038/376348a0

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

Fred Petrif, Rachel H. Giles, Hans G. Dauwerse, Jasper J. Saris, Raoul C.M. Hennekam, Mitsuo Masuno, Niels Tommerup, Gert Jan B. van Ommen, Richard H. Goodman, Dorien J.M. Peters, Martijn H. Breuning

Vollum Institute

Research output: Contribution to journal › Article › peer-review

1059 Scopus citations

Abstract

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 features^1-3. 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-regulated gene expression^9-12. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.

Original language	English (US)
Pages (from-to)	348-351
Number of pages	4
Journal	Nature
Volume	376
Issue number	6538
DOIs	https://doi.org/10.1038/376348a0
State	Published - Jul 27 1995

ASJC Scopus subject areas

General

Access to Document

10.1038/376348a0

Cite this

@article{27d493c956014678bf9457312a7c6c39,

title = "Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP",

abstract = "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-regulated gene expression9-12. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.",

author = "Fred Petrif and Giles, {Rachel H.} and Dauwerse, {Hans G.} and Saris, {Jasper J.} and Hennekam, {Raoul C.M.} and Mitsuo Masuno and Niels Tommerup and {van Ommen}, {Gert Jan B.} and Goodman, {Richard H.} and Peters, {Dorien J.M.} and Breuning, {Martijn H.}",

year = "1995",

month = jul,

day = "27",

doi = "10.1038/376348a0",

language = "English (US)",

volume = "376",

pages = "348--351",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "6538",

}

TY - JOUR

T1 - Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP

AU - Petrif, Fred

AU - Giles, Rachel H.

AU - Dauwerse, Hans G.

AU - Saris, Jasper J.

AU - Hennekam, Raoul C.M.

AU - Masuno, Mitsuo

AU - Tommerup, Niels

AU - van Ommen, Gert Jan B.

AU - Goodman, Richard H.

AU - Peters, Dorien J.M.

AU - Breuning, Martijn H.

PY - 1995/7/27

Y1 - 1995/7/27

N2 - 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-regulated gene expression9-12. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.

AB - 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-regulated gene expression9-12. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.

UR - http://www.scopus.com/inward/record.url?scp=0029022770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029022770&partnerID=8YFLogxK

U2 - 10.1038/376348a0

DO - 10.1038/376348a0

M3 - Article

C2 - 7630403

AN - SCOPUS:0029022770

SN - 0028-0836

VL - 376

SP - 348

EP - 351

JO - Nature

JF - Nature

IS - 6538

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this