Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: Delineation of 7q21.11 breakpoints
Article first published online: 30 JUN 2003
Copyright © 2003 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 124A, Issue 1, pages 10–18, 1 January 2004
How to Cite
Vermeulen, S., Menten, B., Van Roy, N., Van Limbergen, H., De Paepe, A., Mortier, G. and Speleman, F. (2004), Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations: Delineation of 7q21.11 breakpoints. Am. J. Med. Genet., 124A: 10–18. doi: 10.1002/ajmg.a.20378
- Issue published online: 11 DEC 2003
- Article first published online: 30 JUN 2003
- Manuscript Accepted: 16 APR 2003
- Manuscript Received: 16 JUL 2002
- The Fund for Scientific Research—Flanders (Belgium) (Research Grant). Grant Numbers: 1.5.183.02, G.0200.03
- complex chromosomal rearrangements;
Constitutional de novo complex chromosomal rearrangements (CCRs) are a rare finding in patients with mild to severe mental retardation. CCRs pose a challenge to the clinical cytogeneticist: generally CCRs are assumed to be the cause of the observed phenotypic abnormalities, but the complex nature of these chromosomal changes often hamper the accurate delineation of the chromosomal breakpoints and the identification of possible imbalances. In a first step towards a more detailed molecular cytogenetic characterization of CCRs, we studied four de novo CCRs using multicolor fluorescent in situ hybridization (M-FISH), comparative genomic hybridization (CGH), and FISH with region specific probes. These methods allowed a more refined characterization of the breakpoints in three of the four CCRs. The occurrence of 7q breakpoints in three out of these four CCRs and in 30% of reported CCRs suggested preferential involvement of this chromosomal region in the formation of CCRs. Further analysis of these 7q breakpoints revealed a 2 Mb deletion at 7q21.11 in one patient and involvement of the same region in a cryptic insertion in a second patient. This particular region contains at least 5 candidate genes for mental retardation. The other patient had a breakpoint more proximal to this region. The present data together with these from the literature provide evidence that a region within 7q21.11 may be prone to breakage and formation of CCRs. © 2003 Wiley-Liss, Inc.