出生缺陷是由多种因素造成的,比如染色体异常,环境因素,和母性因素。在这项研究中,我们专注于探索一对非近亲夫妇的遗传原因,这些夫妇由于无法解释的复发性胎儿畸形而导致四次妊娠失败,这些胎儿畸形具有相似的症状和正常的染色体拷贝数变异.对这对夫妇和其中一个受影响的胎儿使用三全外显子组测序(trio-WES),我们发现了一个突变,c.1996delC关于受影响的胎儿和丈夫携带的母体印迹基因MAGEL2,导致沙夫阳综合征。为了筛选这个突变,我们进一步进行了植入前遗传学诊断(PGD)策略,然后进行了基因系谱验证和致病性分析.经过PGD筛选的胚胎移植后,1名正常新生儿出生,此前没有异常症状(2019年2月15日).我们提供了第一个数据,该数据在EAS(东亚)数据库中鉴定了Schaaf-Yang综合征胎儿的致病基因(MAGEL2c.1996delC),并根据WES结果对这对夫妇使用经过处理的PGD克服了这种遗传缺陷。
Birth defects are caused by multiple factors, such as chromosome abnormality, environmental factors, and maternal factors. In this study, we focused on exploring the genetic causes of a non-consanguineous couple who suffered from four times of unsuccessful pregnancy due to unexplained recurrent fetal malformations with similar symptoms and normal chromosome copy number variations. Using trio-whole exome sequencing (trio-WES) for this couple and one of the affected fetuses, we found a mutation, c.1996delC on the maternal imprinted gene MAGEL2 that was carried by the affected fetus and husband, leading to Schaaf-Yang syndrome. To screen this mutation, we further performed preimplantation genetic diagnosis (PGD) strategy followed by a gene pedigree validation and pathogenicity analysis. After the transfer of a PGD-screened embryo, a normal newborn without previous abnormal symptoms was born (February 15, 2019). We present the first data that identified a pathogenic gene (MAGEL2 c.1996delC) in a fetus with Schaaf-Yang syndrome in the EAS (East Asian) database and overcame this genetic defect by using processed PGD for this couple based on the WES results.