A novel monogenic preimplantation genetic testing strategy for sporadic polycystic kidney caused by de novo PKD1 mutation
A novel monogenic preimplantation genetic testing strategy for sporadic polycystic kidney caused by de novo PKD1 mutation
复制标题
一种针对PKD1新突变引起的散发性多囊肾的新型单基因植入前基因检测策略
DOI：
10.1111/cge.13871
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发表时间：
2020-11-20
影响因子：
3.5
通讯作者：
Sun, Yingpu
中科院分区：
文献类型：
--
作者：
Shi, Hao;Niu, Wenbin;Sun, Yingpu
常染色体显性遗传性多囊肾病(ADPKD)是最常见的遗传性肾病，可导致终末期肾病和肾功能衰竭。植入前单基因检测(PGT-M)可以有效地防止遗传病在孕前从父母传给后代。然而，PGT-M目前对胚胎的致病基因携带状态采用单核苷酸多态性(SNP)连锁分析，连锁分析需要该家族的先证者。在这里，我们报告了一种新的PGT-M策略，使用单精子SNP连锁分析来治疗由新的PKD1突变引起的男性散发性ADPKD患者。我们招募了5对因新生PKD1突变导致的男性ADPKD夫妇，并从6个PGT-M周期中检测到39个胚胎。这五对夫妇至少有一个胚胎没有携带PKD1突变。在这五对夫妇中，两对夫妇和两对成功分娩的健康胎儿的羊水基因检测证实了胚胎携带者状态的准确性。因此，利用单个精子SNP连锁分析的新的PGT-M策略被证明是可行和有效的，用于治疗由从头PKD1突变引起的男性ADPKD。
Autosomal dominant hereditary polycystic kidney disease (ADPKD) is the most common inherited kidney disease that causes end-stage renal disease and kidney failure. Preimplantation genetic testing for monogenic (PGT-M) can effectively prevent the transmission of genetic diseases from parents to the offspring before pregnancy. However, PGT-M currently adopts the single nucleotide polymorphism (SNP) linkage analysis for embryo's pathogenic gene carrying status and linkage analysis requires proband of the family. Here we report a new PGT-M strategy using single sperm SNP linkage analysis for male patient with sporadic ADPKD caused by de novo PKD1 mutation. We recruited five couples with male patient with ADPKD caused by de novo PKD1 mutation, and 39 embryos from six PGT-M cycles were detected. The five couples had at least one embryo that does not carry the PKD1 mutation. Within these five couples, the accuracy of carrier status of embryos was confirmed by amniotic fluid gene detection of two couples and two couples successfully delivered healthy fetuses. Therefore, the new PGT-M strategy of using single sperm SNP linkage analysis was proved to be feasible and effective for male patient with ADPKD caused by de novo PKD1 mutation.