Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.
Taiwan J Obstet Gynecol. 2020 Jul;59(4):580-585. doi: 10.1016/j.tjog.2020.05.019.
We present prenatal diagnosis and molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (sSMC) at amniocentesis associated with concomitant microduplication of 8q22.1.
A 39-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age, and the result was 47, XY, +mar dn. The woman requested for repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) and DNA methylation analysis were applied to determine the nature of the sSMC.
aCGH on the uncultured amniocytes revealed the result of arr 8q22.1 (93,918,763-96,618,539) × 3.0, arr 15q11.2q13.2 (22,765,628-30,658,876) × 4.0, arr 15q13.2q13.3 (30,653,877-32,509,926) × 3.0 [GRCh37 (hg19)]. Interphase FISH analysis using RP11-34H12 [15q13.2; Texas Red, 30,709,033-30,893,021 (hg19)] on 100 uncultured amniocytes showed that 38 cells had three signals, 45 cells had four signals and 27 cells had two signals. The parental bloods had normal aCGH results. The karyotype of cultured amniocytes was 47, XY, +inv dup(15) (pter→q13::q13→pter) which was confirmed by metaphase FISH analysis. No informative markers could be found in QF-PCR analysis. DNA methylation analysis on cord blood confirmed a maternal origin of the 15q11-q13 gene dosage increase with a result of 15q11.2 SNRPN DNA hypermethylation. Postnatal cytogenetic analysis on cord blood, umbilical cord and placenta showed the results consistent with the prenatal diagnosis.
Molecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome presenting as an sSMC at amniocentesis.
我们介绍了一例近端 15 号染色体倒位重复[inv dup(15)]的产前诊断和分子细胞遗传学特征，该病例在羊膜穿刺术时表现为小额外标记染色体（sSMC），并伴有 8q22.1 的微重复。
一位 39 岁的高龄孕妇因母亲年龄较大而行羊膜穿刺术，结果为 47，XY，+mar dn。该孕妇要求在 20 周时再次进行羊膜穿刺术。应用 array comparative genomic hybridization (aCGH)、荧光原位杂交（FISH）、定量荧光聚合酶链反应（QF-PCR）和 DNA 甲基化分析来确定 sSMC 的性质。
未培养的羊水细胞的 aCGH 结果显示 arr 8q22.1（93,918,763-96,618,539）×3.0、arr 15q11.2q13.2（22,765,628-30,658,876）×4.0、arr 15q13.2q13.3（30,653,877-32,509,926）×3.0[GRCh37（hg19）]。100 个未培养的羊水细胞的间期 FISH 分析使用 RP11-34H12[15q13.2；Texas Red，30,709,033-30,893,021（hg19）]，结果显示 38 个细胞有三个信号，45 个细胞有四个信号，27 个细胞有两个信号。父母的血液 aCGH 结果正常。培养的羊水细胞的核型为 47，XY，+inv dup(15)（pter→q13::q13→pter），这一结果通过中期 FISH 分析得到了证实。QF-PCR 分析未发现有意义的标记。脐血的 DNA 甲基化分析证实了 15q11-q13 基因剂量增加的母源性，结果为 15q11.2 SNRPN DNA 高甲基化。脐血、脐带和胎盘的产后细胞遗传学分析结果与产前诊断一致。
分子细胞遗传学技术可用于快速诊断羊膜穿刺术时表现为 sSMC 的 inv dup(15) 染色体。
