Christian S L, Smith A C, Macha M, Black S H, Elder F F, Johnson J M, Resta R G, Surti U, Suslak L, Verp M S, Ledbetter D H
Diagnostic Development Branch, National Institute of Health, Bethesda, MD 20892-0940, USA.
Prenat Diagn. 1996 Apr;16(4):323-32. doi: 10.1002/(SICI)1097-0223(199604)16:4<323::AID-PD856>3.0.CO;2-5.
Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent of Prader-Willi syndrome cases, is usually caused by maternal meiosis I non-disjunction associated with advanced maternal age. These cases may initially be detected as mosaic trisomy 15 during routine prenatal diagnostic studies. In such cases, PCR (polymerase chain reaction) microsatellite analysis of uncultured cells makes prospective prenatal diagnosis for UPD15 possible with results available in 2-4 days. We have performed molecular analyses on a series of seven cases of mosaic trisomy 15 identified in amniotic fluid (AF, n = 3) or chorionic villus samples (CVS, n = 4) from patients initially referred for advanced maternal age or abnormal triple screen. In all cases, the maternal ages were > or = 35 years and maternal meiosis I non-disjunction was documented as the cause of the trisomy in all informative cases (n = 5). Of the three case with mosaic trisomy 15 at amniocentesis, two showed the presence of the trisomy in the fetus. Molecular analysis showed one case with maternal UPD15 in the euploid cell line and one case with biparental inheritance. Both of these families elected to terminate the pregnancies based on the presence of true fetal mosaicism. In the third case, low-level trisomy 15 mosaicism in the amniotic fluid was not confirmed in a follow-up amniotic fluid sample and molecular analysis indicated biparental inheritance in the fetus. For the four trisomy 15 mosaics detected at CVS, molecular analysis was performed on direct amniotic fluid cell lysates for prospective diagnosis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic analysis of the amniotic fluid in all four cases was normal, indicating confined placental mosaicism. Molecular analysis showed one of these four cases to have maternal heterodisomy 15. Based on the likelihood of Prader-Willi syndrome due to maternal UPD15, the couple chose to terminate the pregnancy. The total of two of seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the theoretical expectation of one-third and indicates a high risk of UPD in such pregnancies. Therefore, UPD testing should be offered in all cases of mosaic trisomy 15 encountered in CVS or amniocentesis.
母源单亲二体15（UPD15）约占普拉德-威利综合征病例的25%，通常由与母亲高龄相关的母源减数分裂I不分离引起。在常规产前诊断研究中，这些病例最初可能被检测为15号染色体三体嵌合体。在此类病例中，对未培养细胞进行聚合酶链反应（PCR）微卫星分析可实现对UPD15的前瞻性产前诊断，2 - 4天即可获得结果。我们对一系列7例在羊水（AF，n = 3）或绒毛膜绒毛样本（CVS，n = 4）中鉴定出的15号染色体三体嵌合体进行了分子分析，这些样本来自最初因母亲高龄或三联筛查异常而转诊的患者。所有病例中，母亲年龄均≥35岁，且在所有信息充分的病例（n = 5）中，母源减数分裂I不分离被记录为三体的病因。在羊水穿刺时发现15号染色体三体嵌合体的3例病例中，2例显示胎儿存在三体。分子分析显示，1例在整倍体细胞系中存在母源UPD15，1例为双亲遗传。基于真正的胎儿嵌合现象，这两个家庭均选择终止妊娠。在第3例中，羊水样本中低水平的15号染色体三体嵌合现象在后续羊水样本中未得到证实，分子分析表明胎儿为双亲遗传。对于在CVS时检测到的4例15号染色体三体嵌合体，在妊娠14 - 16周时对直接羊水细胞裂解物进行分子分析以进行UPD的前瞻性诊断。所有4例病例羊水的后续细胞遗传学分析均正常，表明为局限性胎盘嵌合。分子分析显示这4例病例中有1例存在母源异二体15。基于母源UPD15导致普拉德-威利综合征的可能性，这对夫妇选择终止妊娠。7例15号染色体三体嵌合体中有2例导致UPD15，这与三分之一的理论预期相符，表明此类妊娠中UPD的风险很高。因此，对于在CVS或羊水穿刺中遇到的所有15号染色体三体嵌合体病例，均应进行UPD检测。
