Search

BackgroundsIntramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine.MethodsHealthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions.ResultsEleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline:

Abstract Marinesco‐Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co‐chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 mutations in abnormal corticogenesis of MSS. SIL1‐silencing caused neuronal migration delay during corticogenesis ex vivo. While RNAi‐resistant SIL1 rescued the defects, three MSS‐causing SIL1 mutants tested did not. These mutants had lower affinities to HSPA5 in vitro, and SIL1‐HSPA5 interaction as well as HSPA5 function was found to be crucial for neuronal migration ex vivo. Furthermore time‐lapse imaging revealed morphological disorganization associated with abnormal migration of SIL1‐deficient neurons. These results suggest that the mutations prevent SIL1 from interacting with and regulating HSPA5, leading to abnormal neuronal morphology and migration. Consistent with this, when SIL1 was silenced in cortical neurons in one hemisphere, axonal growth in the contralateral hemisphere was delayed. Taken together, abnormal neuronal migration and interhemispheric axon development may contribute to MR in MSS.