1. ¹Scientific Institute Eugenio Medea, Bosisio Parini, Lecco, Italy
2. ²Department of Neurorehabilitation 2 – Psychopathological Disturbances in Childhood and Adolescence, Scientific Institute Eugenio Medea for Research, Hospitalization and Healthcare, Regional Branch of Ostuni (BR), Ostuni, Italy
3. ³Biologia Generale e Genetica Medica, Università Pavia, Pavia, Italy
4. ⁴IRCCS Policlinico San Matteo, Pavia, Italy

Correspondence: Dr MC Bonaglia, IRCCS Eugenio Medea, Via Don Luigi Monza, 20, Bosisio Parini, Lecco 23842, Italy. Tel: +39 031 877 111; Fax: +39 031 877 499; E-mail: clara.bonaglia@bp.lnf.it

⁵These authors contributed equally to this study.

Received 8 April 2008; Revised 1 July 2008; Accepted 25 July 2008; Published online 24 September 2008.

Abstract

We studied a family in which the same 10 Mb inverted duplication of 2p25.3–p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100 kb resolution array-CGH (aCGH) showed that, beside the duplication, a 273 kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (20 kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680 bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.