**1. Introduction**

34 Bacterial Artificial Chromosomes

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Williams-Beuren syndrome (WBS, MIM No. 194050) is a contiguous gene deletion syndrome that was described independently by Williams et al. (1961) in patients with supravalvular aortic stenosis, growth retardation and an unusual facial appearance (Williams et al., 1961) and by Beuren et al. (1962) in patients having the same features as well as dental anomalies and friendly personality (Beuren et al., 1962).

The clinical picture of WBS includes a characteristic craniofacial dysmorphology with broad forehead, periorbital fullness, flat nasal bridge, broad nasal tip, long philtrum, full lips and lower cheeks, micrognathia, wide mouth and stellate irides, growth retardation, cardiovascular anomalies (mostly supravalvular aortic stenosis and pulmonary artery stenosis), mild to moderate mental retardation and unique behavioral and neurocognitive profile (relative preservation of linguistic abilities and gross visual-spatial processing dysfunction) (Morris et al., 1988; Pober, 2010). Its incidence is estimated at 1/7,500-1/20,000 (Grimm & Wesselhoeft, 1980; Morris et al., 1988; Stromme et al., 2002).

Williams-Beuren syndrome results from the hemizygous deletion of several genes, including *ELN* (elastin), encompassing 1.55 to 1.84 Mb on chromosome 7q11.23 (Ewart et al., 1993; Meng et al., 1998; Pober, 2010; Schubert & Laccone, 2006; Wang et al., 1999). 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).

<sup>\*</sup> Audrey Basinko1,2,3, Nathalie Douet-Guilbert 1,2,3, Séverine Audebert-Bellanger 4, Philippe Parent 4,

Clémence Chabay-Vichot 1,4, Clément Bovo 1,2, Nadia Guéganic 1,2, Marie-Josée Le Bris 3, Frédéric Morel 1,2,3

*<sup>1</sup>Faculté de Médecine et des Sciences de la Santé, Université de Brest, Brest, France 2Institut National de la Santé et de la Recherche Médicale (INSERM), U613, Brest, France 3Service de Cytogénétique, Cytologie et Biologie de la Reproduction, Hôpital Morvan, CHRU Brest, Brest, France 4Département de Pédiatrie et de Génétique Médicale, Hôpital Morvan, CHRU Brest, Brest, France* 

The WBS deletion region is flanked by highly homologous clusters of genes and pseudogenes organized into low-copy-repeat (LCR) blocks. 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).

Several studies have investigated the size of the WBS deletion using multiplex PCR with several microsatellite markers (Brondum-Nielsen et al., 1997; Perez Jurado et al., 1996; Wang et al., 1999; Wu et al., 1998). Most of the patients were found to carry the 1.5 or 1.8 Mb deletion. In the present study, we performed fluorescent *in situ* hybridization (FISH) with Bacterial Artificial Chromosome (BAC) clones in an attempt to map the WBS deletion in 14 WBS patients.
