1. ¹Operative Unit of Medical Genetics, Hospital of Reggio Calabria Az. Ospedaliera Bianchi-Melacrino-Morelli, V Petrara Reggio Calabria, Reggio Calabria, Italy
2. ²Dipartimento di Scienze Ambientali, Seconda Università di Napoli, via Vivaldi 43, Caserta, Italy
3. ³Institute of Genetics and Byophisics A. Bozzati Traverso, Naples, Italy

Correspondence: Dr M Priolo, Operative Unit of Medical Genetics, Hospital of Reggio Calabria Az. Ospedaliera Bianchi-Melacrino-Morelli, Via Malacrino, V Petrara Reggio, Reggio Calabria 89100, Italy. Tel: +39 096 539 7296; Fax: +39 096 539 7350; E-mail: prioloma@libero.it

⁴These authors have contributed equally to this work.

Received 5 September 2007; Revised 30 October 2007; Accepted 11 December 2007; Published online 23 January 2008.

Abstract

Human chromosome 11p15.5 harbours a large cluster of imprinted genes. Different epigenetic defects at this locus have been associated with both Beckwith–Wiedemann syndrome (BWS) and Silver–Russell syndrome (SRS). Multiple techniques (Southern blotting, COBRA and microsatellite analysis) have been used so far to detect various DNA methylation abnormalities, uniparental disomies and copy number variations, which are characteristics of these two diseases. We have now evaluated a methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA) for the molecular diagnosis of BWS and SRS. Seventy-three samples derived from BWS- and SRS-affected individuals and 20 controls were analysed by conventional tests and MS-MLPA in blind. All cases that were found positive with conventional methods were also identified by MS-MLPA. These included cases with paternal UPD11, hyper- or hypo-methylation at the Imprinting Centre 1 or Imprinting Centre 2 and rare 11p15.5 duplications. In summary, this MS-MLPA assay can detect both copy number variations and methylation defects of the 11p15.5 critical region within one single experiment and represents an easy, low cost and reliable system for the molecular diagnostics of BWS and SRS.