Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest
Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest
复制标题
DOI：
10.1016/j.rbmo.2018.03.009
复制
发表时间：
2018-06-01
影响因子：
4
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Wang, Xueqian;Song, Di;Wang, Lei
成功的人类生殖始于正常的配子形成、受精和早期胚胎发育。这些步骤中任何一个步骤的异常都会导致不孕。许多不孕症患者经历了多次IVF和卵胞浆内单精子注射(ICSI)周期的失败，胚胎发育停滞是IVF/ICSI反复失败的常见表型。然而，这种表型的遗传基础还知之甚少。皮质下母体复合体(SCMC)基因在胚胎发育中起重要作用，通过全外显子组测序，在4例胚胎发育停滞患者中发现了SCMC基因TLE6、PADI6和KHDC3L的新的双等位基因突变。在一名卵裂胚胎患者身上发现了TLE6的突变，该患者的胚胎在第三天停止生长，未能形成胚泡。两名胚胎停滞在卵裂阶段的患者有PADI6突变，在一名胚胎停滞在桑拿期的患者中发现了KHDC3L突变。在另外80名患者中，这些基因没有发现突变。这些发现为TLE6、PADI6和KHDC3L在胚胎发育中的重要作用提供了进一步的证据。这项工作为IVF/ICSI复发性失败患者的基因诊断奠定了基础。(C)2018年生殖健康有限公司。爱思唯尔有限公司出版。保留所有权利。
Successful human reproduction initiates from normal gamete formation, fertilization and early embryonic development. Abnormalities in any of these steps will lead to infertility. Many infertile patients undergo several failures of IVF and intracytoplasmic sperm injection (ICSI) cycles, and embryonic developmental arrest is a common phenotype in cases of recurrent failure of IVF/ICSI attempts. However, the genetic basis for this phenotype is poorly understood. The subcortical maternal complex (SCMC) genes play important roles during embryonic development, and using whole-exome sequencing novel biallelic mutations in the SCMC genes TLE6, PADI6 and KHDC3L were identified in four patients with embryonic developmental arrest. A mutation in TLE6 was found in a patient with cleaved embryos that arrested on day 3 and failed to form blastocysts. Two patients with embryos that arrested at the cleavage stage had mutations in PADI6, and a mutation in KHDC3L was found in a patient with embryos arrested at the morula stage. No mutations were identified in these genes in an additional 80 patients. These findings provide further evidence for the important roles of TLE6, PADI6 and KHDC3L in embryonic development. This work lays the foundation for the genetic diagnosis of patients with recurrent IVF/ICSI failure. (C) 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.