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

• DOI: 10.1007/s11427-019-9541-0
• Publication Date: 2019-06-01T06:14:27Z
• Authors: Wei Guo; Yanli Nie; Zhiqiang Yan; Xiaohui Zhu; Yuqian Wang; Shuo Guan; Ying Kuo; Wenxin Zhang; Xu Zhi; Yuan Wei; Liying Yan; Jie Qiao
• Keywords: Male; 0301 basic medicine; DNA Copy Number Variations; Infant, Newborn; Embryonic Development; Proteins; Pedigree; 3. Good health; 03 medical and health sciences; Fetus; Pregnancy; Intellectual Disability; Databases, Genetic; Mutation; Exome Sequencing; Humans; Female; Preimplantation Diagnosis

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.