Validation of Fragile X Screening in the Newborn Population Using a Fit-for-Purpose FMR1 PCR Assay System

Publication date: Available online 19 December 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Stacey Lee, Jennifer L. Taylor, Charles Redmond, Andrew Hadd, Jon A. Kemppainen, Brian C. Haynes, Scott Shone, Donald B. Bailey, Gary J. LathamAbstractNewborn screening is designed for pre-symptomatic identification of serious conditions with effective early interventions. Clinical laboratories must perform prospective pilot studies to ensure that the analytical performance and workflow for a given screening test are appropriate. We assessed the potential to screen newborns for fragile X syndrome, a monogenic neurodevelopmental disorder, by establishing a customized, high-throughput PCR and analysis software system designed to detect fragile X mental retardation 1 gene repeat expansions from dried blood spots. Assay precision, accuracy, sensitivity, and specificity were characterized across the categorical range of repeat expansions. The assay consistently resolved genotypes within three CGG repeats of reference values up to at least 137 repeats and within six repeats for larger expansions up to 200 repeats. Accuracy testing results were concordant with reference results. Full and premutation alleles were detected from sub-nanogram DNA inputs eluted from dried blood spots and from mixtures with down to 1% relative abundance of the respective expansion. Analysis of 963 de-identified newborn dried blood spot samples identified 957 normal and six premutation specimens consis...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research