Low incidence of UPD in spontaneous abortions beyond the 5th gestational week
Low incidence of UPD in spontaneous abortions beyond the 5th gestational week
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DOI：
10.1038/sj.ejhg.5200741
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发表时间：
2001-12-01
影响因子：
5.2
通讯作者：
Rehder, H
中科院分区：
文献类型：
--
作者：
Fritz, B;Aslan, M;Rehder, H
大约15-20%的临床确认的妊娠流产，最常见的是8-12孕周。虽然大多数早期妊娠丢失归因于细胞遗传学异常，但约40%的早期流产的病因仍不清楚。为了确定导致自然流产的其他因素，我们回顾性研究了77例细胞遗传学正常的二倍体自然流产患者的单亲二体（UPD）。在所有病例中，通过绒毛膜/羊膜和/或绒毛膜绒毛的细胞遗传学研究排除了染色体不平衡异常。对于UPD筛查，使用高度多态性标记对流产标本和父母血液的DNA进行微卫星分析，显示两例UPD。分析的标记物的分布表明，在病例1中，9号染色体的母本异二体性（UPhD（9）mat）和在病例2中，21号染色体的父本同二体性（UPiD（21）pat）。所提出的起源机制是UPiD（21）pat中的单体互补和UPhD（9）mat中的三体拯救。在UPhD（9）病例中，观察到化脓性绒毛膜炎，并观察到一个明显生长迟缓的胚胎，头臀长3 cm，无明显外部畸形。UPiD（21）例患者的组织学分析提示原发原基缺损。我们的研究结果表明，不到3%的遗传原因不明的妊娠浪费与总染色体UPD。UPD可能导致人类受孕的原基缺陷。染色体非整倍性校正可以发生在非常早期的卵裂阶段。然而，应该对胎盘镶嵌进行更多的研究，以进一步阐明胎儿UPD的时间和机制。
Approximately 15-20% of all clinically recognised pregnancies abort, most commonly between 8-12 gestational weeks. While the majority of early pregnancy losses is attributed to cytogenetic abnormalities, the aetiology of approximately 40% of early abortions remains unclear. To determine additional factors causing spontaneous abortions we retrospectively searched for uniparental disomies (UPD) in 77 cytogenetically normal diploid spontaneous abortions. In all cases an unbalanced chromosome anomaly was ruled out by cytogenetic investigation of chorionic/amniotic membranes and/or chorionic villi. For UPD screening microsatellite analyses were performed on DNA of abortion specimens and parental blood using highly polymorphic markers showing UPD in two cases. The distribution of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat) in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The originating mechanism suggested was monosomy complementation in UPiD(21)pat and trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis was noted and a distinctly growth retarded embryo of 3 cm crown-rump length showing no gross external malformations. Histological analysis in the case of UPiD(21)pat suggested a primary anlage defect. Our results indicate that less than 3% of genetically unexplained pregnancy wastage is associated with total chromosome UPD. UPD may contribute to anlage defects of human conception. Chromosome aneuploidy correction can occur in very early cleavage stages. More research, however, ought to be performed into placental mosaicism to further clarify timing and mechanisms involved in foetal UPD.