Medical Genetics, University of Pavia, Pavia, Italy.
Hum Mutat. 2012 Jun;33(6):923-9. doi: 10.1002/humu.22050. Epub 2012 Apr 16.
Genome-wide arrays are rapidly replacing conventional karyotyping in postnatal cytogenetic diagnostics and there is a growing request for arrays in the prenatal setting. Several studies have documented 1-3% additional abnormal findings in prenatal diagnosis with arrays compared to conventional karyotyping. A recent meta-analysis demonstrated that 5.2% extra diagnoses can be expected in fetuses with ultrasound abnormalities. However, no consensus exists as to whether the use of genome-wide arrays should be restricted to pregnancies with ultrasound abnormalities, performed in all women undergoing invasive prenatal testing or offered to all pregnant women. Moreover, the interpretation of array results in the prenatal situation is challenging due to the large numbers of copy number variants with no major phenotypic effect. This also raises the question of what, or what not to report, for example, how to deal with unsolicited findings. These issues were discussed at a working group meeting that preceded the European Society of Human Genetics 2011 Conference in Amsterdam. This article is the result of this meeting and explores the introduction of genome-wide arrays into routine prenatal diagnosis. We aim to give some general recommendations on how to develop practical guidelines that can be implemented in the local setting and that are consistent with the emerging international consensus.
全基因组芯片技术正在迅速取代传统的核型分析方法，成为产后细胞遗传学诊断的标准手段，其在产前诊断中的应用也在不断增加。多项研究表明，与传统核型分析相比，全基因组芯片技术在产前诊断中可额外发现 1-3%的异常情况。最近的一项荟萃分析显示，在有超声异常的胎儿中，可额外诊断出 5.2%的异常。然而，对于是否应将全基因组芯片技术的应用仅限于有超声异常的妊娠、对所有行有创性产前检测的妇女进行检测，或提供给所有孕妇，目前尚无共识。此外，由于大量的拷贝数变异没有明显的表型效应，因此产前情况下对全基因组芯片结果的解读具有挑战性。这也提出了一个问题，即应该报告哪些内容，例如如何处理非预期的发现。这些问题在阿姆斯特丹举行的 2011 年欧洲人类遗传学协会会议之前的一个工作组会议上进行了讨论。本文是这次会议的成果，探讨了将全基因组芯片技术引入常规产前诊断的问题。我们的目标是就如何制定可在当地实施且与新兴国际共识一致的实用指南提出一些一般性建议。
