Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.
Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Spain.
Clin Chim Acta. 2015 May 20;445:34-40. doi: 10.1016/j.cca.2015.03.013. Epub 2015 Mar 20.
Several recurrent copy number variants (CNVs) increasing risk to neuropsychiatric diseases have been identified in recent years. They show variable clinical expressivity, being associated with different disorders, and incomplete penetrance. However, due to its very low frequency, the full variety of clinical outcomes associated with each one of these CNVs is unknown. Current methods for detection of CNVs are labor intensive, expensive or not suitable for high throughput analysis. Quantitative interspecies competitive PCR linked to variant minisequencing and detection by mass-spectrometry may overcome these limitations. Here, we present two multiplex assays based on this method to screen for eleven psychiatric risk CNVs, such as 1q21, 16p11.2, 3q29, or 16p13.11 regions, among others. The assays were tested in our collection of 514 schizophrenia patients. Results were compared with MLPA at two CNVs. Additional positive results were confirmed by exome sequencing. A total of fourteen patients were CNV carriers. The method presents high sensitivity and specificity, showing its utility as a cheap, accurate, high throughput screening tool for recurrent CNVs. The method may be very useful for management of psychiatric patients as well as screening of different collections of samples to better identify the full spectrum of clinical variability.
近年来，已经鉴定出了几种增加神经精神疾病风险的复发性拷贝数变异（CNVs）。它们表现出不同的临床表达，与不同的疾病相关联，且不完全外显。然而，由于其非常低的频率，与这些 CNVs 中的每一个相关的全部临床结果的多样性是未知的。目前的 CNVs 检测方法劳动强度大、昂贵或不适合高通量分析。定量种间竞争 PCR 与变体小测序相结合，并通过质谱检测，可能克服这些限制。在这里，我们提出了两种基于这种方法的多重分析，以筛选十一个精神疾病风险 CNVs，如 1q21、16p11.2、3q29 或 16p13.11 区域等。该分析在我们的 514 例精神分裂症患者的样本中进行了测试。结果与 MLPA 在两个 CNVs 上进行了比较。两个额外的阳性结果通过外显子组测序得到了证实。共有 14 名患者为 CNV 携带者。该方法具有较高的灵敏度和特异性，表明其可作为一种廉价、准确、高通量的复发性 CNVs 筛查工具。该方法对于精神疾病患者的管理以及不同样本集的筛查可能非常有用，以更好地识别临床变异性的全貌。
