1. ¹Cytogenetics Laboratory, Medical Genetics Department, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
2. ²Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK
3. ³National Genetics Reference Laboratory (Wessex), Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, UK
4. ⁴Human Genetics Division, Southampton University Hospitals Trust, Southampton, UK
5. ⁵Department of Medical Genetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
6. ⁶Cytogenetics Department, Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK

Correspondence: Dr J Barber, Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, Wiltshire SP2 8BJ, UK. Tel: +44 1722 429 080; Fax: +44 1722 338 095; E-mail: john.barber@salisbury.nhs.uk

Received 1 June 2006; Revised 15 August 2006; Accepted 17 August 2006; Published online 20 September 2006.

Abstract

Large-scale copy number variation that is cytogenetically visible in normal individuals has been described as euchromatic variation but needs to be distinguished from pathogenic euchromatic deletion or duplication. Here, we report eight patients (three families and two individuals) with interstitial deletions of 9q13–q21.12. Fluorescence in situ hybridisation with a large panel of BACs showed that all the deleted clones were from extensive tracts of segmentally duplicated euchromatin, copies of which map to both the long and short arms of chromosome 9. The variety of reasons for which these patients were ascertained, and the phenotypically normal parents, indicates that this is a novel euchromatic variant with no phenotypic effect. Further, four patients with classical euchromatic variants of 9q12/qh or 9p12 were also shown to have duplications or triplications of this segmentally duplicated material common to both 9p and 9q. The cytogenetic boundaries between the segmentally duplicated regions and flanking unique sequences were mapped to 9p13.1 in the short arm (BAC RP11-402N8 at 38.7 Mb) and to 9q21.12 in the long arm (BAC RP11-88I18 at 70.3 Mb). The BACs identified in this study should in future make it possible to differentiate between clinically significant deletions or duplications and euchromatic variants with no established phenotypic consequences.