van den Berg Merel M J, van Maarle Merel C, van Wely Madelon, Goddijn Mariëtte
Department of Obstetrics and Gynaecology, University of Amsterdam, The Netherlands.
Biochim Biophys Acta. 2012 Dec;1822(12):1951-9. doi: 10.1016/j.bbadis.2012.07.001. Epub 2012 Jul 13.
A miscarriage is the most frequent complication of a pregnancy. Poor chromosome preparations, culture failure, or maternal cell contamination may hamper conventional karyotyping. Techniques such as chromosomal comparative genomic hybridization (chromosomal-CGH), array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and quantitative fluorescent polymerase chain reaction (QF-PCR) enable us to trace submicroscopic abnormalities. We found the prevalence of chromosome abnormalities in women facing a single sporadic miscarriage to be 45% (95% CI: 38-52; 13 studies, 7012 samples). The prevalence of chromosome abnormalities in women experiencing a subsequent miscarriage after preceding recurrent miscarriage proved to be comparable: 39% (95% CI: 29-50; 6 studies 1359 samples). More chromosome abnormalities are detected by conventional karyotyping compared to FISH or MLPA only (chromosome region specific techniques), and the same amount of abnormalities compared to QF-PCR (chromosome region specific techniques) and chromosomal-CGH and array-CGH (whole genome techniques) only. Molecular techniques could play a role as an additional technique when culture failure or maternal contamination occurs: recent studies show that by using array-CGH, an additional 5% of submicroscopic chromosome variants can be detected. Because of the small sample size as well as the unknown clinical relevance of these molecular aberrations, more and larger studies should be performed of submicroscopic chromosome abnormalities among sporadic miscarriage samples. For recurrent miscarriage samples molecular technique studies are relatively new. It has often been suggested that miscarriages are due to chromosomal abnormalities in more than 50%, but the present review has determined that chromosomal and submicroscopic genetic abnormalities on average are prevalent in maximally half of the miscarriage samples. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.
流产是妊娠最常见的并发症。染色体标本制备不佳、培养失败或母体细胞污染可能会妨碍传统的核型分析。诸如染色体比较基因组杂交（chromosomal-CGH）、阵列比较基因组杂交（array-CGH）、荧光原位杂交（FISH）、多重连接依赖探针扩增（MLPA）和定量荧光聚合酶链反应（QF-PCR）等技术使我们能够追踪亚微观异常。我们发现，单次散发性流产女性中染色体异常的患病率为45%（95%置信区间：38-52；13项研究，7012个样本）。在先有复发性流产后又经历一次流产的女性中，染色体异常的患病率与之相当：39%（95%置信区间：29-50；6项研究，1359个样本）。与仅使用FISH或MLPA（染色体区域特异性技术）相比，传统核型分析检测到的染色体异常更多，与QF-PCR（染色体区域特异性技术）以及仅使用染色体-CGH和阵列-CGH（全基因组技术）相比，检测到的异常数量相同。当出现培养失败或母体污染时，分子技术可作为一种辅助技术发挥作用：最近的研究表明，通过使用阵列-CGH，可额外检测到5%的亚微观染色体变异。由于样本量小以及这些分子畸变的临床相关性未知，因此应对散发性流产样本中的亚微观染色体异常进行更多且规模更大的研究。对于复发性流产样本，分子技术研究相对较新。人们常认为超过50%的流产是由染色体异常所致，但本综述确定，染色体和亚微观遗传异常平均在最多一半的流产样本中普遍存在。本文是名为“人类生殖失败的分子遗传学”的特刊的一部分。
