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

Abstract

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.

• 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
• Journal: Science China. Life sciences (Sci China Life Sci) Vol. 62 Issue 7 Pg. 886-894 (Jul 2019) ISSN: 1869-1889 [Electronic] China
• PMID: 31152388 (Publication Type: Journal Article)

Chemical References

• MAGEL2 protein, human
• Proteins

Topics

• DNA Copy Number Variations
• Databases, Genetic
• Embryonic Development (genetics)
• Female
• Fetus (physiopathology)
• Humans
• Infant, Newborn
• Intellectual Disability (genetics)
• Male
• Mutation
• Pedigree
• Pregnancy
• Preimplantation Diagnosis
• Proteins (genetics)
• Exome Sequencing