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.