Malan Valérie, Lapierre Jean-Michel, Egloff Matthieu, Goidin Didier, Beaujard Marie-Paule, Maurin Marie-Laure, Attié-Bitach Tania, Bessières Bettina, Bernard Jean-Pierre, Roth Philippe, Stirnemann Julien, Salomon Laurent, Romana Serge, Vekemans Michel, Ville Yves, Turleau Catherine
Service d'Histologie-Embryologie-Cytogx00E9;nx00E9;tique, Hx00F4;pital Necker-Enfants Malades, AP-HP, Paris, France.
Cytogenet Genome Res. 2015;147(2-3):103-10. doi: 10.1159/000442904. Epub 2016 Jan 7.
Cytogenetic microarray analysis is now the first-tier genetic test used in a postnatal clinical setting to explore genomic imbalances in individuals with developmental disability and/or birth defects. However, in a prenatal setting, this technique is not widely implemented, largely because the clinical impact of some copy number variants (CNVs) remains difficult to assess. This limitation is especially true in France where termination of pregnancy for medical reasons may be performed at any stage of gestation. During a period of 15 months, we investigated 382 fetuses presenting with ultrasound anomalies, using a customized microarray designed to avoid the detection of CNVs raising challenges for genetic counseling. After excluding common aneuploidies, 20/374 (5.3%) fetuses had a pathogenic CNV, among which 12/374 (3.2%) could have been detected by karyotyping, whereas 8/374 (2.1%) were cryptic. Within these 374 cases, 300 were ongoing pregnancies at the time of array comparative genomic hybridization (aCGH) testing. For these pregnancies, we detected 18/300 (6%) pathogenic CNVs, among which 6/300 (2%) were cryptic. Using this approach, only 2/300 (0.6%) of the detected CNVs raised difficulties for genetic counseling. This study confirms the added value of this strategy in a prenatal clinical setting to minimize ethical issues for genetic counseling while enhancing the detection of genomic imbalances.
细胞遗传学微阵列分析如今是产后临床环境中用于探究发育障碍和/或出生缺陷个体基因组失衡的一线基因检测方法。然而，在产前环境中，这项技术并未广泛应用，主要是因为一些拷贝数变异（CNV）的临床影响仍难以评估。在法国尤其如此，因为出于医学原因的妊娠终止可在妊娠的任何阶段进行。在15个月的时间里，我们使用定制的微阵列对382例出现超声异常的胎儿进行了研究，该微阵列旨在避免检测到给遗传咨询带来挑战的CNV。排除常见非整倍体后，20/374（5.3%）的胎儿存在致病性CNV，其中12/374（3.2%）可通过核型分析检测到，而8/374（2.1%）是隐匿性的。在这374例病例中，300例在进行阵列比较基因组杂交（aCGH）检测时仍在妊娠中。对于这些妊娠，我们检测到18/300（6%）的致病性CNV，其中6/300（2%）是隐匿性的。采用这种方法，检测到的CNV中只有2/300（0.6%）给遗传咨询带来困难。这项研究证实了该策略在产前临床环境中的附加价值，可在尽量减少遗传咨询伦理问题的同时增强对基因组失衡的检测。
