Giuseppe Merla · Nicola Brunetti-Pierri · Lucia Micale · Carmela Fusco

Received: 23 February 2010 / Accepted: 13 April 2010 / Published online: 1 May 2010 © Springer-Verlag 2010

Abstract Copy number variants (CNVs) of the Williams– Beuren syndrome (WBS) 7q11.23 region are responsible for neurodevelopmental disorders with multi-system involvement and variable expressivity. Typical features of WBS microdeletion comprise a recognizable pattern of facial dysmorphisms, supravalvular aortic stenosis, connective tissue abnormalities, hypercalcemia, and a distinctive neurobehavioral phenotype. Conversely, the phenotype of patients carrying the 7q11.23 reciprocal duplications includes less distinctive facial dysmorphisms and prominent speech delay. The common deletion/duplication ranges in size from 1.5 to 1.8 Mb and encompasses approximately 28 genes. This region is Xanked by low copy repeats (LCRs) with greater than »97% identity, which can mediate non-allelic homologous recombination resulting from misalignment of LCRs during meiosis. A clear genotype– phenotype correlation has been established in WBS only for the elastin gene, which is responsible for the vascular and connective tissue abnormalities. The molecular substrates underlying the other clinical features of 7q11.23 CNVs, including the neurocognitive phenotypes, are still debated. Recent studies suggest that besides the role of the genes in the deleted/duplicated interval, multiple factors such as regulatory sequences, epigenetic mechanisms, parental origin of the CNV, and nucleotide variations in the non-deleted/duplicated allele may be important in determining the variable expressivity of 7q11.23 CNV phenotypes. Here, we review the clinical and molecular Wndings and the recent insights on genomic disorders associated with CNVs involving the 7q11.23 region. Introduction