Application of microdeletion and microduplication screening in preimplantation genetic testing: a case report

Microdeletions and microduplications are chromosomal variants ranging up to 3 Mb in size. These abnormalities often arise spontaneously and have significant clinical implications, including developmental delay and congenital anomalies. Given the resolution of conventional preimplantation genetic testing for aneuploidy is > 5-10 Mb, these clinically significant abnormalities are missed. This study presents two cases where preimplantation genetic testing-whole genome sequencing successfully identified small, clinically significant abnormalities.

In the first case, a couple undergoing in vitro fertilization opted to pursue preimplantation genetic testing-whole genome sequencing. Both the female patient (of East Asian ancestry, 32 years old) and the male patient (of European ancestry, 31 years old) did not disclose any history of genetic conditions. A screen of 50 pathogenic microdeletion and microduplication regions was performed in trophectoderm biopsies, identifying a 1.7-Mb microduplication at Xp22.31, linked to seizures, across multiple samples. The female patient later revealed a history of seizures, previously unaware of a genetic cause, highlighting the clinical relevance of this finding. In the second case, a couple of South Asian ancestry (34-year-old female and 36-year-old male) opted to pursue preimplantation genetic testing-whole genome sequencing for targeted screening of a 412-kb duplication on chromosome 10. Since the duplication had originated de novo in the male patient, the patient lacked informative family members for traditional preimplantation genetic testing probe development and was rejected by other preimplantation genetic testing laboratories. However, preimplantation genetic testing-whole genome sequencing successfully accommodated this region, enabling the identification of unaffected embryos.

Preimplantation genetic testing-whole genome sequencing offers higher chromosomal resolution than conventional preimplantation genetic testing, enabling general microdeletion/duplication screening as well as the detection of difficult chromosomal variations. Patients undergoing in vitro fertilization now have the option to screen for additional clinically relevant conditions and explore family planning solutions for familial complex chromosomal abnormalities.