Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Molecular Diagnostics, New York Genome Center, New York, New York, USA.
Clin Genet. 2023 Aug;104(2):210-225. doi: 10.1111/cge.14365. Epub 2023 Jun 19.
Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.
拷贝数变异 (CNVs) 在人类疾病中起着重要作用。虽然传统上染色体微阵列是检测 CNV 的一线测试方法，但基因组测序 (GS) 的使用正在增加。我们报告了 NYCKidSeq 计划中来自不同儿科队列的 GS 检测到的 CNV 的频率，并强调了其临床影响的具体例子。共有 1052 名（0-21 岁）具有神经发育、心脏和/或免疫缺陷表型的儿童接受了 GS 检测。使用表型驱动的分析，导致 183 名（17.4%）参与者有诊断结果。CNVs 占有诊断结果的参与者的 20.2%（37/183），范围从 0.5kb 到 16Mb。在有诊断结果的参与者（n=183）和多个类别的表型中，有 5/17（29.4%）通过 CNV 发现得到解决，这表明在具有复杂表型的参与者中，诊断性 CNVs 的患病率很高。13 名有诊断性 CNV 的参与者（35.1%）之前的遗传检测没有提供信息，其中 9 名包括染色体微阵列。这项研究表明，GS 可用于可靠地检测具有不同表型的儿科队列中的 CNVs。
