Alberta Spinal Muscular Atrophy Newborn Screening-Results from Year 1 Pilot Project.
Farshad NiriJessie NichollsKelly Baptista WyattChristine WalkerTiffany PriceRhonda KellnStacey HumeJillian ParboosinghMargaret LilleyHanna KolskiRoss RidsdaleAndrew MuranyiJean K MahDennis E BulmanPublished in: International journal of neonatal screening (2023)
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.
Keyphrases
- copy number
- gene therapy
- replacement therapy
- genome wide
- high throughput
- pregnant women
- gestational age
- clinical evaluation
- real time pcr
- electronic health record
- big data
- cord blood
- randomized controlled trial
- advanced non small cell lung cancer
- high resolution
- mass spectrometry
- gene expression
- deep brain stimulation
- deep learning
- epidermal growth factor receptor
- dengue virus
- loop mediated isothermal amplification