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Cell. Mol. Life Sci. 66 (2009) 1178 1197 1420-682X/09/071178-20DOI 10.1007/s00018-008-8401-yhttp://www.birkhauser.ch/CMLS
Web End = Birkh user Verlag, Basel, 2008
Cellular and Molecular Life Sciences
ReviewThe genomic basis of the Williams Beuren syndrome
C. Schubert
Institute of Human Genetics, Georg-August-University of Goettingen, Heinrich-Dueker-Weg 12, 37073 Goettingen (Germany), Fax: +49-551-39 7567, e-mail: [email protected]
Received 11 July 2008; received after revision 15 October 2008; accepted 16 October 2008 Online First 26 November 2008
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 1.51.8 mega base pairs (Mb), encompassing app. 28 genes. For a few genes, a genotypephenotype 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.
Keywords. Williams-Beuren syndrome, non-allelic homologous recombination, deletion, duplication, 7q11.23, elastin gene, supravalvular aortic stenosis, LCR.
Introduction
Clinical symptoms. The Williams-Beuren syndrome (WBS) is a rare genomic disorder (1/7,500 1/20,000) caused by a hemizygous deletion of contiguous genes on chromosome 7q11.23 [1]. It was first described in the nineteen-fifties by Fanconi, Lightwood and Payne as Idiopathic infantile hypercalcaemia with failure to thrive [24]. WBS patients clinically display a characteristic pattern of symptoms including vascular stenosis (predominantly supravalvular aortic stenosis (SVAS)), weakness of connective tissue, a typical face, short stature and mental retardation [57]. Facial symptoms include a wide mouth with full cheeks and full lips and periorbital fullness with a broad forehead.The cardiovascular manifestations comprise SVAS and peripheral artery stenosis, which occur in 75% of affected children [8]. Developmental delay is distinct
in tasks requiring complex visual analysis for receiving information, whereas WBS patients perform better on tasks with auditory input and verbal output [9]. The...