RUBINSTEIN-TAYBI SYNDROME CAUSED BY MUTATIONS IN THE TRANSCRIPTIONAL COACTIVATOR CBP

THE Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with fa cial abnormalities, broad thumbs, broad big toes and mental retardatio n as the main clinical features(1-3). 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 restricte d to a region that contains the gene for the human CREB binding protei n (CBP), a nuclear protein participating co-activator in cyclic-AMP-re gulated gene expression(9-12). We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from poin t mutations in the CBP gene itself. Because the patients are heterozyg ous 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.