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

Area of Science:

• Genetics
• Reproductive Medicine
• Developmental Biology

Background:

• Recurrent fetal malformations can stem from various factors, including genetic causes.
• Normal chromosomal analysis does not exclude underlying genetic defects in recurrent pregnancy loss.
• Identifying specific gene mutations is crucial for understanding and managing inherited conditions.

Purpose of the Study:

• To investigate the genetic etiology of recurrent fetal malformations in a non-consanguineous couple.
• To identify the specific genetic mutation responsible for Schaaf-Yang syndrome in affected fetuses.
• To implement a reproductive strategy to prevent the transmission of the identified genetic defect.

Main Methods:

• Trio-whole exome sequencing (trio-WES) was performed on the parents and an affected fetus.
• Mutation screening for c.1996delC in the MAGEL2 gene was conducted.
• Preimplantation genetic diagnosis (PGD) was utilized for embryo selection.
• Gene pedigree validation and pathogenicity analysis were performed.

Main Results:

• A pathogenic mutation (c.1996delC) in the maternal imprinted gene MAGEL2 was identified, causing Schaaf-Yang syndrome.
• The mutation was present in the affected fetus and the father.
• PGD successfully identified unaffected embryos.
• A healthy infant was born following the transfer of a PGD-screened embryo.

Conclusions:

• The MAGEL2 c.1996delC mutation is a cause of Schaaf-Yang syndrome in the East Asian population.
• Trio-WES is effective in diagnosing rare genetic disorders causing recurrent fetal malformations.
• PGD is a viable strategy to overcome genetic defects like Schaaf-Yang syndrome, enabling healthy births.