Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Taiwan J Obstet Gynecol. 2022 Jul;61(4):684-689. doi: 10.1016/j.tjog.2022.05.005.
We present prenatal diagnosis of mosaic trisomy 18 in a pregnancy with a favorable fetal outcome and maternal uniparental disomy 18.
A 38-year-old, primigravid woman underwent the first amniocentesis at 16 weeks of gestation because advanced maternal age. Amniocentesis revealed a karyotype of 46,XX [22/22] in cultured amniocytes, and 36% mosaicism for trisomy 18 and a maternally inherited Xp22.31 microdeletion by array comparative genomic hybridization (aCGH) in uncultured amniocytes. The second amniocentesis at 18 weeks of gestation revealed 47,XX,+18 [14]/46,XX [36] in cultured amniocytes and 36% mosaicism for trisomy 18 by multiplex ligation-dependent probe amplification (MLPA) P095 in cultured amniocytes. Prenatal ultrasound was normal. The parents were phenotypically normal. The third amniocentesis at 23 weeks of gestation revealed 47,XX,+18 [3]/46,XX [17] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 45%-50% mosaicism for trisomy 18, interphase fluorescence in situ hybridization (FISH) revealed 36% (36/100 cells) mosaicism for trisomy 18, and quantitative fluorescent polymerase chain reaction (QF-PCR) showed mosaic maternal uniparental heterodisomy for chromosome 18 and mosaic trisomy 18 of maternal origin. The fourth amniocentesis at 32 weeks of gestation revealed a karyotype of 46,XX [20/20] in cultured amniocytes, and in uncultured amniocytes, aCGH revealed 50%-60% mosaicism for trisomy 18, FISH revealed 21.8% (22/101 cells) mosaicism for trisomy 18, and non-invasive prenatal testing (NIPT) showed chromosome 18 gene dosage increase in the maternal blood. At 34 weeks of gestation, a 1480-g phenotypically normal baby was delivered. The cord blood had 47,XX,+18 [10]/46,XX [30]. The umbilical cord had 47,XX,+18 [4]/46,XX [36]. The placenta had 47,XX,+18 [40/40], and QF-PCR analysis confirmed trisomy 18 of maternal origin. When follow-up at age four months, the neonate was phenotypically normal, FISH analysis on buccal mucosal cells revealed 2% (2/100 cells) mosaicism for trisomy 18, and the peripheral blood had 47,XX,+18 [18]/46,XX [22]. When follow-up at age eight months, the neonate had normal development, the peripheral blood had 47,XX,+18 [15]/46,XX [25], and the buccal mucosal cells showed maternal uniparental heterodisomy for chromosome 18.
Cytogenetic discrepancy may occur between uncultured and cultured amniocytes in mosaic trisomy 18 at amniocentesis. Cultured amniocytes may present progressive decrease in the levels of mosaicism for trisomy 18 as the fetus grows. Mosaic trisomy 18 at amniocentesis can be associated with a favorable outcome.
我们报告了一例在产前诊断为镶嵌性三体 18 的病例，该病例的妊娠结局良好，且母体存在 18 号染色体单亲二体性。
一名 38 岁的初产妇因高龄接受了第一次羊膜穿刺术，在培养的羊膜细胞中发现核型为 46,XX [22/22]，在未培养的羊膜细胞中通过比较基因组杂交（aCGH）发现 36%的镶嵌性三体 18 和母源性 Xp22.31 微缺失。第二次羊膜穿刺术在妊娠 18 周进行，培养的羊膜细胞中发现 47,XX,+18 [14]/46,XX [36]，通过多重连接依赖性探针扩增（MLPA）P095 在培养的羊膜细胞中发现 36%的镶嵌性三体 18。产前超声正常。父母表型正常。第三次羊膜穿刺术在妊娠 23 周进行，培养的羊膜细胞中发现 47,XX,+18 [3]/46,XX [17]，未培养的羊膜细胞中 aCGH 发现 45%-50%的镶嵌性三体 18，间期荧光原位杂交（FISH）发现 36%（36/100 个细胞）的镶嵌性三体 18，定量荧光聚合酶链反应（QF-PCR）显示染色体 18 的母体单亲二体性和母体来源的镶嵌性三体 18。第四次羊膜穿刺术在妊娠 32 周进行，培养的羊膜细胞中发现核型为 46,XX [20/20]，未培养的羊膜细胞中 aCGH 发现 50%-60%的镶嵌性三体 18，FISH 发现 21.8%（22/101 个细胞）的镶嵌性三体 18，非侵入性产前检测（NIPT）显示母体血液中 18 号染色体基因剂量增加。在妊娠 34 周时，分娩了一名 1480g 的表型正常的婴儿。脐带血中发现 47,XX,+18 [10]/46,XX [30]。脐带中发现 47,XX,+18 [4]/46,XX [36]。胎盘中有 47,XX,+18 [40/40]，QF-PCR 分析证实了母体来源的三体 18。在出生后四个月随访时，新生儿表型正常，口腔黏膜细胞的 FISH 分析发现 2%（2/100 个细胞）的镶嵌性三体 18，外周血中发现 47,XX,+18 [18]/46,XX [22]。在出生后八个月随访时，新生儿发育正常，外周血中发现 47,XX,+18 [15]/46,XX [25]，口腔黏膜细胞显示染色体 18 的母体单亲二体性。
在羊膜穿刺术的镶嵌性三体 18 中，未培养和培养的羊膜细胞之间可能存在细胞遗传学差异。随着胎儿的生长，培养的羊膜细胞中三体 18 的镶嵌程度可能会逐渐降低。羊膜穿刺术的镶嵌性三体 18 可能与良好的妊娠结局相关。
