To explore the genetic causes of abnormal pregnancy caused by pericentric inverted insertion of chromosome 9 and provide guidance for reproduction.

The pregnant woman, her husband and the induced fetal tissues, who underwent induced abortion due to fetal growth restriction and fetal cardiac abnormalities in Chengdu Women′s and Children′s Central Hospital in February 2023, were enrolled in this study. Genetic methods such as chromosome microarray analysis (CMA), peripheral blood G-banding chromosome karyotyping, optical genome mapping (OGM), and fluorescence in situ hybridization (FISH) were used to sequential detect, analyze, and verify the abnormality of chromosome 9 in this family. This study was approved by the Ethics Committee of Chengdu Women′s and Children′s Central Hospital [Approval No. KYLS2023(23)]. Informed consent was obtained from all individuals and guardians of fetal included in this study.

① A 15.459 Mb duplication in the fetal chromosome 9q33.2q34.3 region were detected by CMA in the induced fetal tissues. ② There was no abnormality in the pregnant woman′s chromosome karyotype result, but her husband′s karyotype may be 46, XY, ? ins(9)(p24.3q34.3q33.2) or 46, XY, inv(9)(p24.3q33.2). ③ The husband′s OGM test results showed 9q34.3q33.2 was inversely inserted into chromosome 9p24.3 of the same chromosome, which was further verified by mid-stage FISH analysis. The husband′s accurate karyotype was 46, XY, ins(9)(p24.3q34.3q33.2). ④ The couple chose assisted reproductive technology (ART) for pregnancy assistance, and the results of preimplantation genetic testing (PGT) showed that among their 11 embryos, 2 were normal embryos and could be implanted preferentially.

The 9q33.2q34.3 duplication of fetal tissue comes from the recombinant gametes produced by pericentric inverted insertion of the father′s chromosome 9. The combination of multiple genetic technologies is conducive to the accurate diagnosis of rare chromosomal balanced structural variations, and provides an accurate laboratory data for the assessment risk of recurrence and the selection of fertility mode in offspring.