Successful preimplantation genetic testing for a de novo TP63 mutation using direct detection and embryo-based STR haplotyping in EEC syndrome.

OBJECTIVE

Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is a rare autosomal dominant disorder caused by TP63 variants. De novo mutations challenge preimplantation genetic testing for monogenic disorders (PGT-M) when informative relatives are unavailable. This report describes a proband-independent PGT-M workflow for a de novo TP63 variant.

CASE REPORT: Whole-exome sequencing identified a heterozygous TP63 c.925A > G variant in a 34-year-old male with EEC features, with germline transmission confirmed in sperm DNA. A customized PGT-M workflow combined direct mutation detection with short tandem repeat-based haplotype analysis using informative markers closely linked to TP63. Embryos from three IVF cycles underwent combined PGT-M and preimplantation genetic testing for aneuploidy (PGT-A). Among 17 blastocysts, 6 were low-risk for the TP63 variant, and 2 were euploid. Transfer of one euploid, low-risk embryo resulted in a healthy infant without the pathogenic variant.

CONCLUSION

This case supports the feasibility of a proband-independent PGT-M strategy for de novo TP63-related EEC syndrome.