1. ¹Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Helse Bergen HF, Norway
2. ²Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
3. ³Department of Clinical Medicine, University of Bergen, Bergen, Norway

Correspondence: H Lybæk, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, N-5021 Bergen, Norway. Tel: +47 55 97 70 30/+47 55 97 54 75; Fax: +47 55 97 54 79; E-mail: helle.lybak@helse-bergen.no

Received 13 December 2007; Revised 11 March 2008; Accepted 13 March 2008; Published online 7 May 2008.

Abstract

During a 6-year period, 590 patients suspected of having a minor or cryptic genomic imbalance as the cause of mental retardation with dysmorphic signs +/- malformations have been investigated with high-resolution comparative genomic hybridisation (HR-CGH) in our diagnostic laboratory. Thirty-six patients had a small chromosomal aberration detected by routine karyotyping, and 554 patients had a normal G-banded karyotype. In the latter group, a genomic imbalance was detected by HR-CGH in 40 patients (7.2%): 29 deletions, 3 duplications, 4 unbalanced translocations, and 4 occult trisomy mosaicisms. When microarray-based comparative genomic hybridisation (array-CGH) became available, all HR-CGH-positive samples were also investigated by 1 Mb resolution array-CGH for more precise mapping. From the 514 patients with normal HR-CGH findings, a subset of 20 patients with particularly high suspicion of having a chromosomal imbalance was selected for array-CGH. In four of them (20%), an imbalance was detected: three deletions and one duplication. Of note, 73 out of the 80 array-CGH mapped patients had a de novo chromosomal rearrangement (91%). Taken together, this work provides phenotype–genotype information on 80 patients with minor and cryptic chromosomal imbalances.