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

Newborn screening is designed for presymptomatic 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 (DBSs). 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 subnanogram DNA inputs eluted from DBSs and from mixtures with down to 1% relative abundance of the respective expansion. Analysis of 963 deidentified newborn DBS samples identified 957 normal and 6 premutation specimens, consistent with previously published prevalence estimates. These studies demonstrate that the assay system can support high-throughput newborn screening programs.

Ankle stabilizers affect agility but not vertical jump or dynamic balance performance.

UNLABELLED: Ankle stabilizers can reduce ankle sprain incidence and severity by limiting range of motion. Still whether using them affects performance remains unclear. The authors compared effects of 3 ankle stabilizers, tape, lace-up (Swede-O Ankle Lok), and semirigid (Air-Cast Air-Stirrup) braces, and a nonsupport control on vertical jump (Sargent Jump Test), agility (Right-Boomerang Run test), and dynamic balance (Modified Bass Test) in 10 volunteers (4 males, 6 females; 25.6 ± 2.8 years, 167.8 ± 13.7 cm, 61.4 ± 10.7 kg) using repeated-measures ANOVAs. Participants had similar vertical jump (P = .27; control = 41.40 ± 11.89 cm, tape = 37.90 ± 7.92 cm, Swede-O = 41.40 ± 11.89 cm, Air-Cast = 39.29 ± 10.85 cm) and dynamic balance (P = .08; control = 92.50 ± 2.46, tape = 91.55 ± 3.53, Swede-O = 97.00 ± 5.32, Air-Cast = 89.40 ± 6.08) but differing agility scores (P = .03; control = 13.55 ± 1.35 seconds, tape = 14.03 ± 1.5 seconds, Swede-O = 14.10 ± 1.36 seconds, Air-Cast = 14.14 ± 1.41 seconds). Post hoc tests revealed a significant difference (P = .03) between control and Air-Cast but not between Swede-O (P = .06) or tape (P = .07). Effect size (d) analyses indicated that compared with control, all stabilizers trended to increase agility run times (tape, d = 0.33; Swede-O, d = 0.40; Air-Cast, d = 0.43). Since participants primarily required sagittal plane motion when jumping vertically and had relatively slow directional changes in the dynamic balance test, wearing ankle stabilizers did not hamper jump or balance. However, ankle stabilizers hindered participants' ability to perform quick directional changes required in the agility test, with the most rigid stabilizer (Air-Cast) affecting agility the most. Clinicians should be aware that ankle stabilizers may affect some performance measures (agility) but not others (jumping, balance) and continue examinations in larger cohorts. LEVEL OF EVIDENCE: Therapeutic, Level II.