Sato Taisuke, Samura Osamu, Matsuoka Tomona, Yoshida Masaki, Aoki Hiroaki, Migita Ohsuke, Okamoto Aikou, Hata Kenichiro
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan; Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Eur J Med Genet. 2019 Jun;62(6):103533. doi: 10.1016/j.ejmg.2018.08.014. Epub 2018 Aug 30.
We present a case with discordant results in three prenatal screening methods, with additional genetic analyses. Non-invasive prenatal testing (NIPT) was performed on a 41-year-old Japanese woman at 10 weeks of gestation, and the result was positive for trisomy 18 with high accuracy. Amniocentesis was performed at 16 weeks of gestation. However, the result showed 47,XX,+mar[16]/47,XX,+18[2]. Fetal examination by ultrasound revealed no malformations. After termination of the pregnancy, we performed additional genetic analyses, and confirmed the presence of confined placental mosaicism (CPM). Furthermore, a small supernumerary marker chromosome (sSMC) was detected in fetal cells, which was derived de novo from the centromere of chromosome 18. Single nucleotide polymorphism array analysis revealed that fetal chromosome 18 was inherited with maternal uniparental disomy, with a relatively large copy-neutral loss of heterozygosity, including its centromere. Our genetic analyses strongly indicated the cause of result discrepancy in prenatal testing as incomplete trisomy 18 rescue leading to atypical CPM with a sSMC. These findings also offer insight into the mechanisms by which chromosomal aberrations form during human oogenesis and embryogenesis.
我们报告了一例三种产前筛查方法结果不一致的病例，并进行了额外的基因分析。对一名41岁的日本女性在妊娠10周时进行了无创产前检测（NIPT），结果显示18三体呈高精度阳性。在妊娠16周时进行了羊膜穿刺术。然而，结果显示为47,XX,+mar[16]/47,XX,+18[2]。超声检查胎儿未发现畸形。终止妊娠后，我们进行了额外的基因分析，证实存在局限性胎盘嵌合体（CPM）。此外，在胎儿细胞中检测到一条小的额外标记染色体（sSMC），它是从18号染色体的着丝粒新发而来。单核苷酸多态性阵列分析显示，胎儿18号染色体是由母亲单亲二体遗传而来，包括其着丝粒在内存在相对较大的拷贝中性杂合性缺失。我们的基因分析强烈表明产前检测结果不一致的原因是不完全的18三体挽救导致伴有sSMC的非典型CPM。这些发现也为人类卵子发生和胚胎发生过程中染色体畸变形成的机制提供了见解。
