1. ¹Department of Molecular Medicine, Clinical Genetics Unit, Karolinska Institute, CMM L8:02, Stockholm SE-17176, Sweden
2. ²John F Kennedy Institute, Glostrup, Denmark

Correspondence: Dr J Schoumans, Department of Molecular Medicine, Clinical Genetics Unit, Karolinska Institute, CMM L8:02, Stockholm SE-17176, Sweden. Tel: +46 8 51772521; Fax: +46 8 51773620; E-mail: Jacqueline.schoumans@cmm.ki.se

Received 7 November 2003; Revised 22 December 2003; Accepted 15 January 2004; Published online 17 March 2004.

Abstract

An increasing body of evidence indicates that submicroscopic gene dose alterations may cause mental impairment and malformations. During the last decade, comparative genomic hybridization (CGH) has become a useful tool in the detection and mapping of chromosome aberrations. Modifications of CGH with increased resolution down to 3–5 Mb have been reported and CGH is now offered as a diagnostic procedure in the evaluation of patients with idiopathic mental retardation (MR). In order to increase the resolution, we modified the CGH protocol using freshly prepared high-quality metaphase slides and chemical labeling, and tested the method on a set of patients with well-defined submicroscopic chromosome abnormalities with confirmed size 1.3–20.5 Mb. Subsequently, a completely blinded test was performed to compare the performance of the chemical labeling CGH to the commercially available HR-CGH. Using the two different CGH methods, we were able to detect chromosome imbalances down to 2–3 Mb approximately. The HR-CGH method detected all aberrations >6 Mb and a few smaller, while the modified CGH method was able to detect all but three aberrations >1.8 Mb. The modified CGH method was superior in the detection of terminal imbalances, while the HR-CGH software was more successful in the detection of imbalances located very close to the centromeric regions. In conclusion, the resolution of metaphase CGH may be as high as 2–3 Mb but is most likely depending on the chromosomal region involved, a clear limitation when used as a screening method for chromosome aberrations in patients with idiopathic MR.