Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.
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. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3 (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-AMP-regulated gene expression. 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.
Petrij
F
F
Department of Human Genetics, Leiden University, Sylvius Laboratories, The Netherlands.
Giles
R H
RH
Dauwerse
H G
HG
Saris
J J
JJ
Hennekam
R C
RC
Masuno
M
M
Tommerup
N
N
van Ommen
G J
GJ
Goodman
R H
RH
Peters
D J
DJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D050882:CREB-Binding Protein; D002461:Cell Line, Transformed; D016386:Chromosome Walking; D002885:Chromosomes, Human, Pair 16; D003360:Cosmids; D004247:DNA; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics*; D017384:Sequence Deletion; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D050882:CREB-Binding Protein; C494363:CREBBP protein, human