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 suffer...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.展开更多
基金supported by the National Natural Science Foundation of China(31522034,81521002,81730038)the National High Technology Research and Development Program(2015AA020407)
文摘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.
