The genomic basis of the Williams – Beuren syndrome

Abstract

. The Williams-Beuren syndrome is a genomic disorder (prevalence: 1/7,500 to 1/20,000), caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Typical symptoms comprise supravalvular aortic stenosis, mental retardation, overfriendliness and visuospatial impairment. The common deletion sizes range of 1.5–1.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotype-phenotype correlation has been established. The best-explored gene within this region is the elastin gene; its haploinsufficiency causes arterial stenosis. The region of the Williams-Beuren syndrome consists of a single copy gene region (~1.2 Mb) flanked by repetitive sequences – Low Copy Repeats (LCR). The deletions arise as a consequence of misalignment of these repetitive sequences during meiosis and a following unequal crossing over due to high similarity of LCRs. This review presents an overview of the Williams-Beuren syndrome region considering the genomic assembly, chromosomal rearrangements and their mechanisms (i.e. deletions, duplications, inversions) and evolutionary and historical aspects.

Case report of sudden death in a child with Williams syndrome following administration of anaesthesia

“…9 Studies subsequently showed that the deletion of approximately 28 genes is responsible for the phenotypic characteristics. 10 The diagnosis can be confirmed with FISH using commercial probes but currently quantitive realtime polymerase chain reaction (PCR) or multiplex ligation-dependent probe amplification (MLPA) is becoming more useful to predict the phenotype in an individual affected with the syndrome.…”

Defining the Deletion Size in Williams-Beuren Syndrome by Fluorescent In Situ Hybridization with Bacterial Artificial Chromosomes

“…WBS usually results from de novo deletion. Twenty-six to 28 genes have been identified within the WBS deletion region (Merla et al, 2010;Pober, 2010;Schubert, 2009). …”

“…Unequal meiotic recombination during meiosis can lead to deletion of the WBS region. The unique genetic architecture of the region explains why the size of WBS deletion is almost the same in most of the patients (Baumer et al, 1998;Dutly & Schinzel, 1996;Pober, 2010;Schubert, 2009;Valero et al, 2000).…”

Williams–Beuren Syndrome

“…Williams-Beuren syndrome (WBS) is a developmental disorder caused by a hemizygous recurrent deletion of the WBS critical region (WBSCR) at chromosomal band 7q11.23, which includes ELN (gene coding for elastin) and 27 additional coding genes [1]. The common deletion results from recombination between misaligned low copy repeat (LCR) sequences flanking the critical region.…”

“…The deletion occurs between proximal and medial LCRs in about 95% of WBS cases, and it occurs between proximal and distal LCRs in the remaining cases. The size of the deletion is approximately 1.55 Mb for the small deletion and approximately 1.84 Mb for the larger one [1][2][3][4][5]. However, the precise size depends upon the exact position of the breakpoints in each block.…”