Faculty of Medicine, Institute of Human Genetics, University of Belgrade, Belgrade, Serbia.
J Clin Lab Anal. 2022 Jun;36(6):e24441. doi: 10.1002/jcla.24441. Epub 2022 Apr 20.
Array-based genomic analysis is a gold standard for the detection of copy number variations (CNVs) as an important source of benign as well as pathogenic variations in humans. The introduction of chromosomal microarray (CMA) has led to a significant leap in diagnostics of genetically caused congenital malformations and neurodevelopmental disorders, with an average diagnostic yield of 15%. Here, we present our experience from a single laboratory perspective in four years' postnatal clinical CMA application.
DNA samples of 430 patients with congenital anomalies and/or neurodevelopmental disorders were analyzed by comparative genome hybridization using oligonucleotide-based microarray platforms. Interpretation of detected CNVs was performed according to current guidelines. The detection rate (DR) of clinically significant findings (pathogenic/likely pathogenic CNVs) was calculated for the whole cohort and isolated or combined phenotypic categories.
A total of 140 non-benign CNVs were detected in 113/430 patients (26.5%). In 70 patients at least one CNV was considered clinically significant thus reaching a diagnostic yield of 16.3%. The more complex the phenotype, including developmental delay/intellectual disability (DD/ID) as a prevailing feature, the higher the DR of clinically significant CNVs is obtained. Isolated congenital anomalies had the lowest, while the "dysmorphism plus" category had the highest diagnostic yield.
In our study, CMA proved to be a very useful method in the diagnosis of genetically caused congenital anomalies and neurodevelopmental disorders. DD/ID and dysmorphism stand out as important phenotypic features that significantly increase the diagnostic yield of the analysis.
基于阵列的基因组分析是检测拷贝数变异 (CNV) 的金标准，CNV 是人类良性和致病性变异的重要来源。染色体微阵列 (CMA) 的引入使得遗传性先天性畸形和神经发育障碍的诊断取得了重大飞跃，平均诊断率为 15%。在这里，我们从单个实验室的角度介绍了四年临床 CMA 应用的经验。
采用基于寡核苷酸的微阵列平台，对 430 名先天性畸形和/或神经发育障碍患者的 DNA 样本进行比较基因组杂交分析。根据现行指南对检测到的 CNV 进行解读。计算了整个队列以及孤立或联合表型类别中临床显着发现（致病性/可能致病性 CNV）的检出率 (DR)。
在 430 名患者中，共检测到 140 个非良性 CNV，其中 113 名（26.5%）患者存在非良性 CNV。在 70 名患者中，至少有一个 CNV 被认为具有临床意义，从而达到了 16.3%的诊断率。表型越复杂，包括以发育迟缓/智力障碍 (DD/ID) 为主要特征的患者，具有临床意义的 CNV 的检出率越高。单纯性先天性畸形的检出率最低，而“畸形加”类别的检出率最高。
在我们的研究中，CMA 被证明是诊断遗传性先天性畸形和神经发育障碍的非常有用的方法。DD/ID 和畸形是重要的表型特征，可显着提高分析的诊断率。
