Department of Obstetrics and Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
PLoS One. 2019 Nov 21;14(11):e0225457. doi: 10.1371/journal.pone.0225457. eCollection 2019.
Thalassemia and hemoglobinopathy is a group of hereditary blood disorder with diverse clinical manifestation inherited by autosomal recessive manner. The Beta thalassemia/Hemoglobin E disease (HbE/βthal) causes a variable degree of hemolysis and the most severe form of HbE/βthal disease develop a lifelong transfusion-dependent anemia. Preimplantation genetic testing (PGT) is an established procedure of embryo genetic analysis to avoid the risk of passing on this particular condition from the carrier parents to their offspring. Preimplantation genetic testing for chromosomal aneuploidy (PGT-A) also facilitates the selection of embryos without chromosomal aberration resulting in the successful embryo implantation rate. Herein, we study the clinical outcome of using combined PGT-M and PGT-A in couples at risk of passing on HbE/βthal disease. The study was performed from January 2016 to December 2017. PGT-M was developed using short tandem repeat linkage analysis around the beta globin gene cluster and direct mutation testing using primer extension-based mini-sequencing. Thereafter, we recruited 15 couples at risk of passing on HbE/βthal disease who underwent a combined total of 22 IVF cycles. PGT was performed in 106 embryos with a 3.89% allele drop-out rate. Using combined PGT-M and PGT-A methods, 80% of women obtained satisfactory genetic testing results and were able to undergo embryo transfer within the first two cycles. The successful implantation rate was 64.29%. PGT accuracy was evaluated by prenatal and postnatal genetic confirmation and 100% had a genetic status consistent with PGT results. The overall clinical outcome of successful live birth for couples at risk of producing offspring with HbE/βthal was 53.33%. Conclusively, combined PGT-M and PGT-A is a useful technology to prevent HbE/βthal disease in the offspring of recessive carriers.
地中海贫血和血红蛋白病是一组遗传性血液疾病，具有多种临床表现，呈常染色体隐性遗传方式。β地中海贫血/血红蛋白 E 病（HbE/βthal）导致不同程度的溶血，最严重的 HbE/βthal 疾病会发展为终身依赖输血的贫血。植入前遗传学检测（PGT）是一种胚胎遗传分析的既定程序，可避免携带者父母将这种特殊情况遗传给后代的风险。植入前染色体非整倍体遗传学检测（PGT-A）也有助于选择无染色体异常的胚胎，从而提高胚胎着床成功率。在此，我们研究了在有 HbE/βthal 疾病遗传风险的夫妇中联合使用 PGT-M 和 PGT-A 的临床结果。该研究于 2016 年 1 月至 2017 年 12 月进行。PGT-M 使用短串联重复连锁分析β珠蛋白基因簇周围的区域，并用基于引物延伸的小测序进行直接突变检测。此后，我们招募了 15 对有 HbE/βthal 疾病遗传风险的夫妇，他们共进行了 22 个 IVF 周期。对 106 个胚胎进行了 PGT，等位基因缺失率为 3.89%。使用联合 PGT-M 和 PGT-A 方法，80%的女性获得了满意的基因检测结果，并能够在前两个周期内进行胚胎移植。着床成功率为 64.29%。通过产前和产后遗传确认评估 PGT 准确性，100%的遗传状态与 PGT 结果一致。有遗传风险的夫妇生育 HbE/βthal 患儿的活产总成功率为 53.33%。综上所述，联合 PGT-M 和 PGT-A 是预防隐性携带者后代患 HbE/βthal 疾病的有效技术。
