. 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.

This is the first report on mutations in the laminin, integrin, and ILK system in human cardiomyopathy, which has consequences for endothelial cells as well as for cardiomyocytes, thus providing a new genetic basis for dilated cardiomyopathy in humans.

Williams-Beuren syndrome (WBS) is a rare genetic disorder (1/20000-50000) and is usually caused by a 1.5-to 1.8-Mb heterozygous deletion on chromosome 7q11.23. At least 25 genes have been identified in the deletion region in WBS patients, which is flanked by large low-copy-repeat sequences (>320 kb). By using FISH as well as microsatellite analysis, it is not possible to get a precise identification of the size of the deletion. For determining the deletion size, we developed a reliable quantitative PCR approach. Our assay screens 2.5 Mb of the WBS region in 100-to 300-kb intervals. This methodology has been tested in DNA samples of 65 patients with the clinical suspicion of WBS. In every case we were able to exclude or to identify the presence of a deletion and to determine its size. Deletion size varied from 0.2 Mb to 2.5 Mb. The 2.5-Mb rearrangement represents the largest deletion described at present and it was detected in a severely affected patient. We report the detection efficiency of this new system and the genotype/phenotype correlation.

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