Genetic testing and PGD for unexplained recurrent fetal malformations with MAGEL2 gene mutation  

作　　者：Wei Guo Yanli Nie Zhiqiang Yan Xiaohui Zhu Yuqian Wang Shuo Guan Ying Kuo Wenxin Zhang Xu Zhi Yuan Wei Liying Yan Jie Qiao 

机构地区：[1]Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [2]Key Laboratory of Assisted Reproduction,Ministry of Education,Beijing 100191,China [3]Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction,Beijing 100191,China [4]Bering Advanced Innovation Center for Genomics,Peking University,Beijing 100871,China [5]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China

出　　处：《Science China(Life Sciences)》2019年第7期886-894,共9页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(31522034,81521002,81730038);the National High Technology Research and Development Program(2015AA020407)

摘　　要：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.1996 delC 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.1996 delC) 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.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.1996 delC 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.1996 delC) 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.

关 键 词：UNEXPLAINED RECURRENT fetal MALFORMATIONS whole EXOME sequencing (WES) PREIMPLANTATION genetic diagnosis (PGD) Schaaf-Yang syndrome 

分 类 号：Q[生物学]