Recombination in a balanced complex translocation of a mother leading to a balanced reciprocal translocation in the child. Review of 60 cases of balanced complex translocations

Abstract

We report an unusual case of a balanced reciprocal translocation with a recombinant chromosome which has arisen from a familial balanced complex translocation. Fluorescence in situ hybridization studies were essential for the identification of the breakpoints. A review of 60 cases of balanced complex translocations (BCT) has revealed three cases similar to ours. Carriers of BCT have a high risk of having spontaneous abortions or a child with an unbalanced karyotype. Certain types of balanced rearrangements involving an insertion can give rise to a simpler balanced translocation as a result of crossover. Our observations support the assumption that the chance that a de novo balanced complex translocation is associated with an abnormal phenotype increases with the number of breakpoints.

Recombinant balanced and unbalanced translocations as a consequence of a balanced complex chromosomal rearrangement involving eight breakpoints in four chromosomes

“…2,9 These cases can be divided into three groups. 8 1 simple three-way translocations with an additional pericentric inversion in one of the chromosomes; Actually, recombination has been observed in only six of the 60 reports with the possibility of producing recombinant offspring, and all six belong to the group 3 described by Madan et al 8 The karyotype of the father described in our report also belongs to this group with as many as two chromosomes made up of segments of three different chromosomes (derivative 18 with segments of chromosomes 6, 7, and 18; derivative 21 with segments of chromosomes 7, 18, and 21). The breakpoints are such that a cross-over in the inserted segments would usually lead to an unbalanced and, with only one exception, a balanced karyotype.…”

“…Only six families with recombination derived from a parental CCR have been reported [4][5][6][7][8][9] In the first five reports all offspring had an apparently balanced karyotype showing maternal transmission, with the exception of one report with paternal transmission. 6 Zahed et al 9 were the second authors to report recombination with paternal transmission leading, for the first time, to offspring with an unbalanced karyotype.…”

Meiotic outcomes of three-way translocations ascertained in cleavage-stage embryos: refinement of reproductive risks and implications for PGD

“…A 20% risk of live-born offspring with an unbalanced translocation and an up to 50% risk of miscarriage have been recommended as appropriate general risk figures, 21 which is largely based on the obstetric history of female heterozygotes. 4,29 Due to spermatocyte arrest, very few male three-way translocation heterozygotes are likely to conceive without assisted conception; due to small numbers caution is advised but accepting a higher incidence of 3:3 alternate products, it could be appropriate to consider a lower general risk figure of around 3% (probably between 1 and 8%, Supplementary Appendix VIII) for live birth with chromosome imbalance. However, we suggest that a risk specific for each translocation, estimated using the method we have outlined (Supplementary Appendix III), is more useful in helping a couple decide whether PGD is preferable to natural pregnancy and prenatal diagnosis.…”

“…2 These can include: (i) two separate simple rearrangements in the same individual (double translocation), (ii) terminal exchanges involving three chromosomes with one breakpoint in each chromosome (three-way translocation), and (iii) more complex rearrangements with multiple breakpoints and often involving different types of rearrangement (terminal exchange, inversion, interstitial insertion, deletion) and more than three chromosomes. 3,4,5 Constitutional CCRs are very rare and around 255 cases have been described. 6 A patient with an apparently balanced de novo CCR and learning difficulties and/or multiple congenital abnormalities may have chromosome imbalance (cryptic or sub-microscopic) associated with the rearranged chromosomes or elsewhere in the genome.…”

Les remaniements chromosomiques complexes

“…En 1997, Madan et al [6] ont étoffé cette classification structurale en y intégrant la présence additionnelle d'inversions, d'insertions ou de délétions. Cela a permis d'intégrer les translocations dites insertionnelles à la famille des CCR.…”