II. Molecular basis of the phenomenon
- Live birth prevalence of ABSCRs is estimated around 0,8%-1%. 15-20 % of which occur de novo, and 80-85 % are inherited.
- Most individuals with ABSCRs have a normal phenotype. However, the risk for abnormalities exists. It is relatively low in inherited cases, but high in de novo cases (Table 1).
TABLE 1: Patients with an apparently balanced chromosome rearrangement
|Risk of an abnormal phenotype*|
|De novo cases||
|*Risk: proband excluded in familial cases|
|**MR: mental retardation, MCA: major congenital abnormalities|
- De novo rearrangements represent a challenge in prenatal diagnosis given that the risk of malformations and learning disabilities is about 5-10%.
- In patients with an abnormal phenotype, ABSCRs host “cryptic” chromosomal rearrangements (more often deletions, rarely duplications), uncovered by molecular cytogenetics techniques, mainly the array CGH (Table 2).
TABLE 2: Patients with an abnormal phenotype
|De novo cases||
|*In de novo cases with complex ABSCRs (with more than 3 breakpoints), imbalance was found in 90 %|
- Conversely, patients with a normal phenotype and ABSCRs were found to carry no imbalance.
- The majority of de novo imbalances have a paternal chromosome origin.
- ABSCRs breakpoints were compared in patients with normal and abnormal phenotype:
No significant differences were found in GC contents, nor in the number of CpG islands, the number of genes, exons and genes disrupted, the number of segmental duplications and copy number variants in the 200 Kb window around and within the breakpoints.
Only the number of breakpoints in G-bands versus R-bands was statistically significant (p < 0.01): patients with one or both breakpoints within R-bands had more often an abnormal phenotype.
The proportion of gene disruption (at the breakpoints) was similar in patients with normal and abnormal phenotypes. However, genes implicated in biological processes of the nervous system, genes for transcription/regulation of transcription or signal transduction/signalling, and genes associated with known Mendelian diseases were more frequently disrupted in patients with an abnormal phenotype.
|Written||03-2009||Jean Marie Rival|
|Medical genetic service - CHU Nantes, France|
|This paper should be referenced as such :|
|Rival JM . Apparently balanced structural chromosome rearrangements (ABSCRs) and abnormal phenotype. Atlas Genet Cytogenet Oncol Haematol. March 2009 .|
URL : http://AtlasGeneticsOncology.org/Educ/BalancedRearAbnorID30071ES.html
This paper is referenced by INIST as such :
|http://documents.irevues.inist.fr/bitstream/2042/44697/1/03-2009-BalancedRearAbnorID30071ES.pdf [ Bibliographic record ]|
|© Atlas of Genetics and Cytogenetics in Oncology and Haematology||indexed on : Sat Mar 9 12:10:36 CET 2013|
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