Application of preimplantation genetic testing for monogenic disorders in families with hereditary epilepsy

Acta Universitatis Medicinalis Anhui 2025, 09, v.60 1725-1729     font:big middle small

Found programs: Research Project of Anhui Provincial Institute of Translational Medicine ( No.2021zhyx-C18) ; Natural Science Foundation of Anhui Province ( No.1908085MH270)

Authors:Zhang Wenxiang,Chen Dawei,Wang Tianjuan,Cao Yunxia

Keywords:hereditary epilepsy; whole-exome sequencing; PCDH19 gene;LGI1 gene; preimplantation genetic testing for monogenic disorders; pedigree study;

DOI:10.19405/j.cnki.issn1000-1492.2025.09.021

〔Abstract〕 Objective To evaluate the clinical efficacy of preimplantation genetic testing for monogenic disorders(PGT-M) in families with hereditary epilepsy. Methods Whole-exome sequencing(WES) and familial co-segregation analysis were performed to validate the pathogenicity of variants(PCDH19 c. 1031C > G and LGI1 c. 856T >G) in two monogenic epilepsy families. A clinical PGT-M pathway was implemented,and reproductive outcomes were tracked. Results In Family 1(PCDH19 likely pathogenic variant),13 blastocysts were biopsied over two ovarian stimulation cycles,yielding 3 unaffected euploid embryos(23. 1%). After the third frozen embryo transfer,a healthy male infant was successfully delivered. Prenatal diagnosis confirmed that the fetus did not carry the pathogenic variant PCDH19. Family 2(LGI1 variant of uncertain significance,VUS) screened 14 blastocysts,identifying 2 unaffected euploid embryos(14. 3%),with the first transfer unsuccessful. A clinical pregnancy was currently ongoing following the second frozen-thawed embryo transfer(FET). Conclusion PGT-M can precisely block the vertical transmission of monogenic epileptic pathogenic variants,offering an effective reproductive intervention strategy for families with hereditary epilepsy.