The mechanism of disease in FHS is suspected to be dominant-negative [3] due to the non-random clustering of truncating mutations in the final exon that result in the loss of the major transactivation function of SRCAP located in a 655 residue C-terminal fragment, evidence that expression of a construct solely consisting of the CBP interaction domain of SRCAP strongly inhibits CREB-mediated transactivation in a dominant-negative fashion [5], and the existence of patients with haploinsufficiency of SRCAP who do not have features of FHS [3]. The gene discussed is CREB1; the disease is Floating-Harbor syndrome.