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This article, published in the journal Neuropediatrics, discusses the role of autophagy in cellular clearance and the degradation of specific substrates. The authors focus on the RNaseL pathway and its activation by 2′,5′-oligoadenylate synthetase proteins (OAS) in response to viral RNA. They present clinical, molecular, and imaging data from four patients with biallelic variants in OAS2, highlighting the association of these variants with skeletal dysplasia, neurodevelopmental disorders, and immunodeficiency. The study also includes experimental findings from cellular assays and proteomics, as well as single cell RNA sequencing. The authors conclude that biallelic OAS2 variants may be a novel candidate gene for developmental disorders and suggest a close relationship between deficient innate immune response and autophagy in monogenic neuroimmunological disorders. [Extracted from the article]

Purpose: We describe the development of an observational video coding tool, the Rehabilitation Observation Measure of Engagement (ROME), to quantify engagement in rehabilitative settings at the person (internal state of an individual) and between-system (interaction between individuals) level., Methods: Forty-nine children with unilateral spastic cerebral palsy (29 males; Age: M  = 9.28 yrs, SD = 3.08 yrs) and their interventionists were videotaped during different activities. Construct validity was examined by correlating the ROME with the Engagement vs. Disaffection with Learning Survey and the Pediatric Rehabilitation Intervention Measure of Engagement - Observation questionnaire. Inter- and intra-rater reliability were examined using two independent raters. The ROME's responsiveness to change was examined by comparing scores across activities., Results: For construct validity, results showed a positive correlation for person-level engagement ( r  = 0.444, p  = 0.003). No relationship was found between-system-level engagement. High intrarater (91.8%) and interrater (96.1%) reliability was found. The ROME's responsiveness to change was supported by children exhibiting lower engagement scores during repetitive shaping activities., Conclusion: These findings provide evidence that the ROME is a reliable tool to objectively examine the construct of engagement within rehabilitation and is valid for quantifying person-level engagement. It provides information that cannot be extracted from questionnaires and can help guide intervention decisions.

Biallelic variants in the Golgi SNAP receptor complex member 2 gene ( GOSR2 ) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2 -related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient, a female homozygous for the GOSR2 founder variant p.Gly144Trp, showed only mild fine motor developmental delay and generalized tonic-clonic seizures triggered by infections during adolescence, with seizure remission on levetiracetam. The associated movement disorder progressed atypically slowly during adolescence compared to its usual speed, from initial intention tremor and myoclonus to ataxia, hyporeflexia, dysmetria, and dystonia. These findings expand the genotype-phenotype spectrum of GOSR2 -related disorders and suggest that GOSR2 should be included in the consideration of monogenetic causes of dystonia, global developmental delay, and seizures.