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.

Retrospective testing of respiratory specimens for COVID-19 to assess for earlier SARS-CoV-2 infections in Alberta, Canada.

Background: The first case of coronavirus disease 2019 (COVID-19) in Alberta, Canada, was confirmed on March 5, 2020. Because the virus testing criteria had changed significantly over this time period, we wanted to ascertain whether previous cases of COVID-19 had been missed in the province. Methods: Our aim was to retrospectively evaluate specimens submitted for respiratory virus testing from December 1, 2019, through March 7, 2020, for undetected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections before the first confirmed case. Results: Testing of 23,517 samples (representing 23,394 patients) identified 1 patient positive for SARS-CoV-2. This specimen was collected on February 24, 2020, from a patient with symptoms consistent with COVID-19 who had recently returned from the western United States. Phylogenetic analysis confirmed this viral isolate belonged to lineage B.1. The epidemiology of this case is consistent with those of other early cases before sustained community transmission, which included a travel history outside of Canada. Conclusion: This exercise provides support that local public health pandemic planning was satisfactory and timely.

Historique: Le premier cas de maladie à coronavirus 2019 (COVID-19) en Alberta, au Canada, a été confirmé le 15 mars 2020. Puisque les critères de dépistage ont beaucoup évolué pendant cette période, les chercheurs voulaient vérifier si des cas antérieurs de COVID-19 avaient été omis dans la province. Méthodologie: Les chercheurs ont procédé à l'évaluation rétrospective d'échantillons soumis en vue du dépistage d'un virus respiratoire entre le 1er décembre 2019 et le 7 mars 2020, afin de retracer les infections par le coronavirus 2 du syndrome respiratoire aigu sévère (SARS-CoV-2) non décelées avant le premier cas confirmé. Résultats: Le dépistage de 23 517 échantillons (représentant 23 394 patients) a fait ressortir un patient positif au SARS-CoV-2. Le prélèvement avait été effectué le 24 février 2020 chez un patient éprouvant des symptômes correspondant à la COVID-19 revenu récemment de l'ouest des États-Unis. L'analyse phylogénétique a confirmé que l'isolat viral appartenait à la lignée B.1. L'épidémiologie de ce cas est compatible avec celle des autres premiers cas précédant une transmission communautaire soutenue, qui incluait un voyage à l'extérieur du Canada. Conclusion: Cet exercice appuie la pertinence et la rapidité de la planification sanitaire locale de la pandémie.

Coordinated changes in classes of ribosomal protein gene expression is associated with light-induced retinal degeneration.

PURPOSE: To identify genes with altered expression levels in the degenerating retina in a light-induced retinal degeneration (LIRD) model. METHODS: Adult Sprague-Dawley rats were exposed to intense green light for 4 hours. After this treatment, the retinas were excised, RNA was extracted, and a cDNA library was prepared. The cDNA library was differentially cross-screened with probes representing 0-hour and 4-hour light-exposed rat retina. Transcripts with altered expression levels were sequenced and expression was confirmed by Northern blot analysis. Gene-specific primers were designed and used to examine the expression levels of other genes involved in protein synthesis. Promoter sequences of the ribosomal-binding protein (Rbp) genes were analyzed for transcription-binding sites. RESULTS: Of the 10,000 clones that were initially screened, 41 exhibited altered expression levels. Six of these corresponded to five known Rbp genes. Six additional Rbp genes were also examined. In total, 9 of 11 Rbp genes exhibited an increase in expression levels in response to a 4-hour light exposure. In contrast, the transcript levels of elongation factor 1alpha1 and 18S rRNA did not increase. The most abundant transcription factor-binding sites conserved in the promoter regions of all Rbp genes examined in this study include AP-1, Oct-1, V-myb, USF, Pax-4, and the FOX family of transcription factors. CONCLUSIONS: The results indicate that light-induced retinal degeneration (LIRD) is associated with increased expression of specific Rbp genes. These Rbp genes may be involved in mediating visual cell loss in LIRD through a translational or an extraribosomal mechanism.