Analytical and Clinical Validity Study of FirstStepDx PLUS: A Chromosomal Microarray Optimized for Patients with Neurodevelopmental Conditions

• Published in: PLoS currents 2017-02, Vol.9
• Main Authors: Hensel, Charles, Vanzo, Rena, Martin, Megan, Dixon, Sean, Lambert, Christophe, Levy, Brynn, Nelson, Lesa, Peiffer, Andy, Ho, Karen S, Rushton, Patricia, Serrano, Moises, South, Sarah, Ward, Kenneth, Wassman, Edward
• Format: Article
• Language: English
• Subjects: Evidence on Genomic Tests
• ISSN: 2157-3999; 2157-3999
• DOI: 10.1371/currents.eogt.7d92ce775800ef3fbc72e3840fb1bc22

Chromosomal microarray analysis (CMA) is recognized as the first-tier test in the genetic evaluation of children with developmental delays, intellectual disabilities, congenital anomalies and autism spectrum disorders of unknown etiology. To optimize detection of clinically relevant copy number variants associated with these conditions, we designed a whole-genome microarray, FirstStep  PLUS (FSDX). A set of 88,435 custom probes was added to the Affymetrix CytoScanHD platform targeting genomic regions strongly associated with these conditions. This combination of 2,784,985 total probes results in the highest probe coverage and clinical yield for these disorders. Clinical testing of this patient population is validated on DNA from either non-invasive buccal swabs or traditional blood samples. In this report we provide data demonstrating the analytic and clinical validity of FSDX and provide an overview of results from the first 7,570 consecutive patients tested clinically. We further demonstrate that buccal sampling is an effective method of obtaining DNA samples, which may provide improved results compared to traditional blood sampling for patients with neurodevelopmental disorders who exhibit somatic mosaicism.