Oneda Beatrice, Baldinger Rosa, Reissmann Regina, Reshetnikova Irina, Krejci Pavel, Masood Rahim, Ochsenbein-Kölble Nicole, Bartholdi Deborah, Steindl Katharina, Morotti Denise, Faranda Marzia, Baumer Alessandra, Asadollahi Reza, Joset Pascal, Niedrist Dunja, Breymann Christian, Hebisch Gundula, Hüsler Margaret, Mueller René, Prentl Elke, Wisser Josef, Zimmermann Roland, Rauch Anita
Institute of Medical Genetics, University of Zurich, Zurich, Switzerland.
Prenat Diagn. 2014 Jun;34(6):525-33. doi: 10.1002/pd.4342. Epub 2014 Mar 21.
The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics.
We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing.
High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion.
High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance.
本研究的目的是首次确定高分辨率微阵列检测在常规产前诊断中的可靠性和诊断能力。
我们对464例细胞遗传学正常且有任何侵入性检测指征的产前样本应用了高分辨率染色体微阵列检测。
高分辨率检测显示，胎儿超声异常病例和高龄产妇（AMA）病例的诊断率分别为6.9%和1.6%，这与之前使用低分辨率微阵列的研究结果相似。在另外3例（0.6%）有AMA指征的病例中，检测到易感性风险位点的畸变。此外，1例（0.2%）女性胎儿显示X连锁畸变，这一发现与未来的计划生育相关。我们发现，因解读未报告的拷贝数变异而必须对父母进行检测的病例率（3.7%）以及意义不明的剩余变异率（0.4%）低至可接受水平。值得注意的是，在专家遗传咨询后，这些发现并未导致终止妊娠。0.4%的局限性胎盘嵌合体发生率与传统核型分析观察到的发生率相似，且特别涉及一例胎盘微缺失病例。
高分辨率产前微阵列检测是一种可靠的技术，与传统核型分析相比，其诊断率至少提高了17.3%，且意义不确定的变异频率没有增加。
