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

PLoS Curr. 2017 Feb 27;9:ecurrents.eogt.7d92ce775800ef3fbc72e3840fb1bc22. doi: 10.1371/currents.eogt.7d92ce775800ef3fbc72e3840fb1bc22.


Introduction: 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.

Array design: To optimize detection of clinically relevant copy number variants associated with these conditions, we designed a whole-genome microarray, FirstStepDx 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.

Results and discussion: 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.

Grant support

The work described was funded entirely by Lineagen, Inc., the developer of FSDX. Lineagen provided support in the form of salaries for authors CH, RV, MM, SD, KH, MS, and ERW. Author AP is an employee of the University of Utah and a paid consultant to Lineagen. Authors LN and KW are employees of Affiliated Genetics, Inc., a contract service laboratory performing FSDX tests. Author BL is an employee of Columbia University Medical Center, a contract service laboratory performing FSDX tests. Author SS is a paid consultant to Lineagen, a current employee of 23&Me, and was previously an employee of ARUP, a contract service laboratory conducting tests for Lineagen at the time of this study. Author CL is a faculty member at the University of New Mexico and a paid consultant to Lineagen. These funders did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.