Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations : delineation of 7q21.11 breakpoints

Vermeulen, Stefan; Menten, Björn; Van Roy, Nadine; Van Limbergen, Heidi; De Paepe, Anne; Mortier, Geert; Speleman, Frank

doi:10.1002/AJMG.A.20378

Title

Molecular cytogenetic analysis of complex chromosomal rearrangements in patients with mental retardation and congenital malformations : delineation of 7q21.11 breakpoints

Author

Vermeulen, Stefan

Menten, Björn

Van Roy, Nadine

Van Limbergen, Heidi

De Paepe, Anne

Mortier, Geert

Speleman, Frank

Abstract

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.

Language

English

Source (journal)

American journal of medical genetics : part A. - Bognor Regis, 2003, currens

Publication

Bognor Regis : 2004

ISSN

1552-4825 [print]

1552-4833 [online]

DOI

10.1002/AJMG.A.20378

Volume/pages