Laboratory of Medical Genetics, Medical School, National and Kapodistrian University of Athens, St. Sophia's Children's Hospital, 11527 Athens, Greece.
Genes (Basel). 2023 Jul 25;14(8):1519. doi: 10.3390/genes14081519.
Chromosomal microarray analysis (CMA) is considered a first-tier test for patients with developmental disabilities and congenital anomalies and is also routinely applied in prenatal diagnosis. The current consensus size cut-off for reporting copy number variants (CNVs) in the prenatal setting ranges from 200 Kb to 400 Kb, with the intention of minimizing the impact of variants of uncertain significance (VUS). Very limited data are currently available on the application of higher resolution platforms prenatally. The aim of this study is to investigate the feasibility and impact of applying high-resolution CMA in the prenatal setting. To that end, we report on the outcomes of applying CMA with a size cut-off of 20 Kb in 250 prenatal samples and discuss the findings and diagnostic yield and also provide follow-up for cases with variants of uncertain significance. Overall, 19.6% (49) showed one or more chromosomal abnormalities, with the findings classified as Pathogenic (P) or Likely Pathogenic (LP) in 15.6% and as VUS in 4%. When excluding the cases with known familial aberrations, the diagnostic yield was 12%. The smallest aberration detected was a 32 Kb duplication of the 16p11.2 region. In conclusion, this study demonstrates that prenatal diagnosis with a high-resolution aCGH platform can reliably detect smaller CNVs that are often associated with neurodevelopmental phenotypes while providing an increased diagnostic yield, regardless of the indication for testing, with only a marginal increase in the VUS incidence. Thus, it can be an important tool in the prenatal setting.
染色体微阵列分析（CMA）被认为是发育障碍和先天性异常患者的一线检测方法，也常用于产前诊断。目前，产前报告拷贝数变异（CNV）的共识大小截断值范围为 200 Kb 至 400 Kb，目的是最小化意义不明的变异（VUS）的影响。目前，关于在产前应用更高分辨率平台的应用数据非常有限。本研究旨在探讨在产前应用高分辨率 CMA 的可行性和影响。为此，我们报告了在 250 个产前样本中应用大小截断值为 20 Kb 的 CMA 的结果，并讨论了发现和诊断率，并为意义不明的变异病例提供了随访。总体而言，19.6%（49 个）显示出一种或多种染色体异常，其中 15.6%的发现被归类为致病性（P）或可能致病性（LP），4%的发现被归类为 VUS。当排除已知家族性异常的病例时，诊断率为 12%。检测到的最小异常是 16p11.2 区域的 32 Kb 重复。总之，本研究表明，高分辨率 aCGH 平台的产前诊断可以可靠地检测到与神经发育表型相关的较小 CNV，同时提供更高的诊断率，无论检测的指征如何，VUS 的发生率仅略有增加。因此，它可以成为产前诊断的重要工具。
