Abstract
We studied a family in which the same 10Mb inverted duplication of 2p25.3-p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100kb resolution array-CGH (aCGH) showed that, beside the duplication, a 273kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (∼20kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.
| Original language | English |
|---|---|
| Pages (from-to) | 179-186 |
| Number of pages | 8 |
| Journal | European Journal of Human Genetics |
| Volume | 17 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2009 |
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ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the genesis of inverted duplications. / Bonaglia, Maria Clara; Giorda, Roberto; Massagli, Angelo; Galluzzi, Rita; Ciccone, Roberto; Zuffardi, Orsetta.
In: European Journal of Human Genetics, Vol. 17, No. 2, 2009, p. 179-186.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the genesis of inverted duplications
AU - Bonaglia, Maria Clara
AU - Giorda, Roberto
AU - Massagli, Angelo
AU - Galluzzi, Rita
AU - Ciccone, Roberto
AU - Zuffardi, Orsetta
PY - 2009
Y1 - 2009
N2 - We studied a family in which the same 10Mb inverted duplication of 2p25.3-p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100kb resolution array-CGH (aCGH) showed that, beside the duplication, a 273kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (∼20kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.
AB - We studied a family in which the same 10Mb inverted duplication of 2p25.3-p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100kb resolution array-CGH (aCGH) showed that, beside the duplication, a 273kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (∼20kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.
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U2 - 10.1038/ejhg.2008.160
DO - 10.1038/ejhg.2008.160
M3 - Article
C2 - 18813332
AN - SCOPUS:58349104960
VL - 17
SP - 179
EP - 186
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 2
ER -