Chromatin remodeling complexes alter chromatin structure to control access to DNA and therefore control cellular processes such as transcription, DNA replication, and DNA repair. CECR2 is a chromatin remodeling factor that plays an important role in neural tube closure and reproduction. Loss-of-function mutations in Cecr2 result primarily in perinatal lethal neural tube defect exencephaly, with non-penetrant mice that survive to adulthood exhibiting subfertility. CECR2 forms a complex with ISWI proteins SMARCA5 and (or) SMARCA1; however, further information on the structure and function of the complex is not known. Therefore, we identified candidate components of the CECR2-containing remodeling factor (CERF) complex in embryonic stem (ES) cells using mass spectroscopy. Both SMARCA5 and SMARCA1 were confirmed to be present in the CERF complexes in ES cells and testes. However, the novel proteins CCAR2 and LUZP1 are CERF components in ES cells, but not in the testis. This tissue specificity in mice suggests that these complexes may also have functional differences. Furthermore, LUZP1, the loss of which is also associated with exencephaly, appears to play a role in stabilizing the CERF complex in ES cells.

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.