The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways.
Altogether, these results reveal a pivotal role for BAZ1B in neurodevelopment and implicate its haploinsufficiency as a likely contributor to the neurological phenotypes in WS.
Williams syndrome transcription factor (WSTF), which is encoded by the BAZ1B gene, was first identified as a hemizygously deleted gene in patients with Williams syndrome.
In the light of this new development we discuss the role of one of the deleted genes in WBS, Williams syndrome transcription factor (WSTF), in the etiology of hypercalcaemia in WBS.
Given the inappropriate appearance of regions of heterochromatin in BAZ1B knockout cells, it is evident that WSTF performs a critical role in maintaining chromatin and transcriptional states, a property that is likely compromised by WSTF haploinsufficiency in WBS patients.
Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS.
By making WSTF-deficient mice, some of the heart defects as well as abnormal calcium metabolism observed in Williams syndrome are attributed to the abnormal chromatin remodeling activity caused by WSTF deficiency.
Loss of WSTF expression resulted in neonatal lethality, and all WSTF(-/-) neonates and approximately 10% of WSTF(+/-) neonates suffered cardiovascular abnormalities resembling those found in autosomal-dominant Williams syndrome patients.
The Williams Syndrome Transcription Factor (WSTF), the product of the WBSCR9 gene, is invariably deleted in the haploinsufficiency Williams-Beuren Syndrome.
Haploinsufficiency for WBSCR9 gene products may contribute to the complex phenotype of WBS by interacting with tissue-specific regulatory factors during development.