The use of arrays to detect copy‐number variations in clinical practice

Since their introduction, array-based detection techniques have flooded diagnostic practice worldwide. Technical innovation and commercialization of array platforms have brought down their costs and put them within reach of many diagnostic laboratories. Array diagnostics are, therefore, rapidly replacing traditional karyotyping techniques for a range of indications. Such innovations give rise to many questions related to indications for testing, test outcome interpretation, quality control, and the ethics of using arrays for particular applications. There is a growing need for guidelines on these topics. To address the key issues in this field, an international workshop was organized in Amsterdam in 2011 under the auspices of the Genetic Services Quality Committee of the European Society of Human Genetics. The aim was to explore whether consensus could be achieved on the major quality issues and to produce recommendations for the use of arrays to detect copy-number variations (CNVs) in a diagnostic setting. The outcome of the workshop has been summarized in five articles that formulate recommendations and guidelines to cover the different aspects of CNV detection using diagnostic arrays in genetics. In general, it can be concluded that genome-wide array analysis is well established in postnatal cytogenetics. Most commercially available platforms and data analysis software packages are of high quality and relatively easy to use. The article by Vermeesch et al. (2012) aims to guide laboratories in assuring the quality of their array experiments, by suggesting standards for the minimal resolution of the platform used, and for the interpretation and reporting of the results. Unfortunately, the interpretation of CNVs is not always straightforward since the distinction between pathogenic and benign variants can be difficult as, for example, CNVs with a highly variable phenotype and incomplete penetrance are common. Webbased databases, especially when used in combination, can be helpful in interpreting CNVs. A general clinical interpretation strategy for CNVs is presented by de Leeuw et al. (2012). Because of the genome-wide nature of the use of arrays, clinically relevant CNVs will be detected that are not related to the patient’s known phenotype. This clearly raises ethical questions, which may be especially complex if the tested individuals are children, investigated prenatally or postnatally. Dondorp et al. (2012) discuss these ethical issues, trying to find a solution to possible “information overload” in counseling, and exploring the balance between the “right to know” and the “right not to know” in different situations. Two particular clinical applications of array diagnostics are discussed in more detail. Vetro et al. (2012) explore the use of arrays in prenatal diagnosis and provide recommendations for the various