Cytogenetic PGD Department, Arnaud De Villeneuve Hospital, Montpellier, France.
Cytogenetic PGD Department, Arnaud De Villeneuve Hospital, Montpellier, France.
Reprod Biomed Online. 2019 Jul;39(1):40-48. doi: 10.1016/j.rbmo.2019.02.010. Epub 2019 Mar 12.
To analyse why unbalanced viable offspring are derived mainly from the 3:1 segregation mode in t(11;22)(q23;q11.2) reciprocal translocation.
Retrospective analysis of 24 pre-implantation genetic testing for chromosomal structural re-arrangements (PGT-SR) cycles was performed on seven male and five female carriers of t(11;22) translocation. Sperm analysis was performed on each male carrier. These patients were directed to the study centre after several years of miscarriages and/or abortions, primary infertility for male carriers or birth of an affected child.
Twenty-four PGT-SR cycles were performed to exclude imbalances in both male and female carriers. The unbalanced embryos derived from the adjacent-1 segregation mode were the most represented in both male and female carriers (68.4% and 50%, respectively). These results were positively related with meiotic segregation analysis of reciprocal translocation in spermatozoa. A thorough analysis of the unbalanced embryo karyotypes determined that the expected viable +der22 karyotype resulting from 3:1 malsegregation was less represented at 5.3%.
These findings highlight the divergence that may exist between meiotic segregation and post-zygotic selection. Post-zygotic selection would be responsible for the elimination of unbalanced embryos derived from the adjacent-1 segregation mode. The combined action of several factors occurs at the beginning of post-zygotic selection. Genetic counselling must consider the risk of a birth related to the adjacent-1 segregation mode, irrespective of the sex of the translocation carrier. These results will allow deeper understanding of the PGT results of t(11;22) carriers, which often include a high number of aneuploid embryos.
分析为什么不平衡的可育胚胎主要来自 t(11;22)(q23;q11.2)相互易位的 3:1 分离模式。
对 7 名男性和 5 名女性 t(11;22)易位携带者的 24 个胚胎植入前染色体结构重排（PGT-SR）周期进行回顾性分析。对每位男性携带者进行精子分析。这些患者在多次流产和/或流产、男性携带者原发性不育或生育受影响的孩子后多年来被引导到研究中心。
进行了 24 次 PGT-SR 周期以排除男性和女性携带者的不平衡。来自相邻-1 分离模式的不平衡胚胎在男性和女性携带者中最为常见（分别为 68.4%和 50%）。这些结果与精子减数分裂相互易位的分离分析呈正相关。对不平衡胚胎核型的深入分析表明，预期的来自 3:1 错误分离的可育+der22 核型的代表率较低，为 5.3%。
这些发现强调了减数分裂分离和合子后选择之间可能存在的差异。合子后选择负责消除来自相邻-1 分离模式的不平衡胚胎。合子后选择的开始涉及几个因素的共同作用。遗传咨询必须考虑到与相邻-1 分离模式相关的出生风险，而不论易位携带者的性别如何。这些结果将有助于更深入地了解 t(11;22)携带者的 PGT 结果，其中经常包括大量非整倍体胚胎。
