Simultaneous trophectoderm biopsies enable preimplantation genetic testing for monogenic disorders in de novo case of incontinentia pigmenti: case report.

Simultaneous trophectoderm biopsies may enable preimplantation genetic testing in challenging cases of de novo incontinentia pigmenti, but further research is needed to confirm these findings.

Summary and findings

This case report describes the use of two simultaneous trophectoderm biopsies for preimplantation genetic testing for monogenic disorders in a 29-year-old woman with de novo incontinentia pigmenti. The procedure resulted in the successful development of a PGT-M test and the generation of 10 euploid embryos that tested negative for the IKBKG deletion. No therapeutic claims are made.

Abstract

Objective To describe the use of two simultaneous trophectoderm biopsies as a method to establish linkage analysis for preimplantation genetic testing for monogenic disorders (PGT-M) test development in a case of de novo incontinentia pigmenti (IP). Design Case report. Subject A 29-year-old nulligravid woman with de novo IP, confirmed to have the common, large deletion of exons 4-10 in the IKBKG gene. Negative maternal testing confirmed the mutation was de novo in our patient. Exposure Two simultaneous trophectoderm biopsies from a minimum of four embryos were obtained to enable two independent deoxyribonucleic acid preparations. This approach was utilized to complete linkage analysis, facilitating successful test development for PGT-M. Main outcome measures PGT-M test development and subsequent intracytoplasmic sperm injection/PGT-M cycle targeting the IKBKG deletion. Results PGT-M test development was successful. The patient underwent two antagonist stimulation protocols with intracytoplasmic sperm injection and PGT-M, yielding 10 euploid embryos that tested negative for the IKBKG deletion and were deemed suitable for transfer. Conclusions PGT-M for de novo IP is particularly challenging given the presence of the IKBKGP1 pseudogene, its terminal location, and the fact that indirect linkage analysis is necessary for large gene deletions. Without genetic information from parents and offspring, PGT-M test development is frequently unsuccessful. This case demonstrates that simultaneous trophectoderm biopsies can enable PGT-M in otherwise ineligible cases, offering a viable path forward for patients affected by de novo IP.

Limitations

Not reported in abstract.

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