Alberta Spinal Muscular Atrophy Newborn Screening-Results from Year 1 Pilot Project.

Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by biallelic pathogenic/likely pathogenic variants of the survival motor neuron 1 (SMN1) gene. Early diagnosis via newborn screening (NBS) and pre-symptomatic treatment are essential to optimize health outcomes for affected individuals. We developed a multiplex quantitative polymerase chain reaction (qPCR) assay using dried blood spot (DBS) samples for the detection of homozygous absence of exon 7 of the SMN1 gene. Newborns who screened positive were seen urgently for clinical evaluation. Confirmatory testing by multiplex ligation-dependent probe amplification (MLPA) revealed SMN1 and SMN2 gene copy numbers. Six newborns had abnormal screen results among 47,005 newborns screened during the first year and five were subsequently confirmed to have SMA. Four of the infants received SMN1 gene replacement therapy under 30 days of age. One infant received an SMN2 splicing modulator due to high maternally transferred AAV9 neutralizing antibodies (NAb), followed by gene therapy at 3 months of age when the NAb returned negative in the infant. Early data show that all five infants made excellent developmental progress. Based on one year of data, the incidence of SMA in Alberta was estimated to be 1 per 9401 live births.

Toward optimal detection of the common prenatal aneuploidies by quantitative fluorescent-polymerase chain reaction: comparison of two commercial assays.

BACKGROUND/AIM: To evaluate and compare the performance of the recently released Aneufast™ v2 (MolgentixSL) and QST*RplusV2 commercial assays (Gen-Probe), both designed for the quantitative fluorescent-polymerase chain reaction (PCR) detection of the common aneuploidies during pregnancy. METHODS: A series of 160 consecutive fetal samples referred for rapid aneuploidy detection testing and an additional 25 samples enriched for the presence of an abnormality were selected for comparison. RESULTS: To confidently rule out a chromosome abnormality, a second round of short tandem repeat typing was required for 14.1% (26) and 9.7% (18) of the specimens analyzed with Aneufast v2 and QST*RplusV2, respectively. Reflex testing was required for 7.6% (14) and 5.9% (11) of the specimens analyzed with respective assays to confidently rule out an autosomal trisomy. For the sex chromosomes, the difference in the amount of follow-up testing is greater between the assays, as a result of the inclusion in the initial PCR of the TAF9L paralogous marker in the QST*RplusV2 assay. CONCLUSIONS: Overall, both assays performed similarly in the detection of aneuploidies. In this sample set, the QST*RplusV2 kit required less frequent reflex testing, which translates into shorter turnaround time and cost savings. The incorporation of the TAF9L paralogous sequence in the initial PCR is advantageous for diagnostic use.