Atypical Deletion of Williams-beuren Syndrome Reveals the Mechanism of Neurodevelopmental Disorders

Abstract

Background The Williams-Beuren syndrome (WBS) is a multiple phylogenetic disorder, caused by the hemizygous deletion of 1.55 to 1.84 Mb on chromosome 7q11.23, which encodes a fragment of 26 to 28 genes. Among these genes, the deletion of the elastin (ELN) gene haplotype is the main cause of cardiovascular abnormalities. Other genes, such as CLIP2, GTF2IRD1, and GTF2I, may be associated with specific cognitive and craniofacial features. However, genes associated with specific neurocognitive phenotypes are still controversially discussed. The purpose of this study is to further explore the mechanism of neurodevelopmental disorders in patients with Williams-Beuren syndrome.Patients and methods Patients who had been diagnosed with WBS were recruited. The deletion was precisely defined by chromosome microarray analysis and the clinical phenotype was evaluated. Results This study identified nine patients with atypical deletions from 111 patients with WBS. One patient had normal neurodevelopmental with deletion of Williams-Beuren syndrome chromosomal region (WBSCR) telomere side genes, including GTF2I and GTF2IRD1, while another patient retained these genes but showed neurodevelopmental abnormalities. Seven of the eight patients with the WBSCR22 gene deletion developed growth restriction.Conclusions By comparing the genotype and phenotype of patients with typical deletions and atypical deletions, the deletion of GTF2I and GTF2IRD1 genes alone insufficient to induce typical neurocognitive phenotypes in WBS patients. The BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS. Furthermore, the deletion of the WBSCR22 gene may be the main cause of physical growth restriction in WBS patients.

Striatal Syntaxin 1A Is Associated with Development of Tourette Syndrome in an Iminodipropionitrile-Induced Animal Model

“…Recently, it has been revealed that native vesicle docking can be mediated by a single trans binary Sx1A-Sb2 complex in the absence of SNAP25 [39,40]. And STX1A may be involved in Williams-Beuren syndrome and Parkinson's disease [41,42]. To date, the link between STX1A and dopaminergic neurons is not fully disclosed.…”