Hood et al, are reporting in the AJHG that SRCAP is causing Floating-Harbor Syndrome. Exome sequencing in five unrelated individuals identified mutations in SRCAP ; all are tightly clustered within a small (111 codon) region of the final exon. The results were further verified by identifying mutations in 8 more patients. In all the instances in which parental DNA was available, all mutations have been shown to be de novo. SRCAP is an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREB-binding protein (CREBBP is the major cause of Rubinstein-Taybi syndrome). The mutations are predicted to abolish three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact. These findings show that SRCAP mutations are the major cause of Floating-Harbor Syndrome and offer an explanation for the clinical overlap between Floating-Harbor Syndrome and Rubinstein-Taybi syndrome.

Periklis Makrythanasis, MD, PhD

Hood et al, Am J Hum Genet. 2012 Jan 18. [Epub ahead of print]

OMMBID Chapter 248 : Rubinstein-Taybi Syndrome