SNP arrays in Beckwith-Wiedemann syndrome: An improved diagnostic strategy

作者：Keren Boris; Chantot Bastaraud Sandra; Brioude Frederic; Mach Corinne; Fonteneau Eric; Azzi Salah; Depienne Christel; Brice Alexis; Netchine Irene; Le Bouc Yves; Siffroi Jean Pierre; Rossignol Sylvie^*

来源：European Journal of Medical Genetics, 2013, 56(10): 546-550.

DOI：10.1016/j.ejmg.2013.06.005

• Beckwith-Wiedemann syndrome
• 11p15 paternal disomy
• SNP array
• Mosaicism

Beckwith-Wiedemann syndrome is an overgrowth disorder with an increased risk of childhood tumors that results from a dysregulation of imprinted gene expression in the 11p15 region. Since epigenetic defects are the most frequent anomalies, first-line diagnostic methods involve methylation analysis. When paternal isodisomy is suspected, it should be confirmed by a second technique capable of distinguishing true 11p15 paternal disomy (patUPD) from paternal 11p15 duplication or 11p15 trisomy. We sought to evaluate the interest of using SNP arrays in the Beckwith-Wiedemann syndrome diagnostic strategy. We analyzed the SNP profiles of 25 Beckwith Wiedemann patients with previously determined methylation indexes. Among them, 3 had 11p15 trisomies, 13 had patUPD, 8 had an inconclusive methylation index and 1 had a normal result. All known trisomies and known patUPDs were detected. Moreover we found 7 low-rate mosaicisms 11p15 patUPDs among the 8 patients with an inconclusive methylation index. We were able to precisely characterize the sizes and mosaicism rates of the anomalies. We demonstrate that SNP arrays are of real diagnostic interest in Beckwith-Wiedemann syndrome: 1) they help to distinguish patUPDs from trisomies more precisely than karyotyping and FISH, 2) they help determine the size and mosaicism rate of patUPDs, 3) they provide complementary information in inconclusive cases, helping to distinguish low-rate patUPD mosaicism from other BWS-related molecular defects.

• 出版日期2013-10