Okur-Chung Neurodevelopmental Syndrome (OCNDS) is caused by heterozygous mutations to the CSNK2A1 gene, which encodes the alpha subunit of casein kinase II (CK2). The most frequently occurring mutation is lysine 198 to arginine (K198R). To investigate the impact of this mutation, we first generated a high-resolution phosphorylation motif of CK2WT, including the first characterization of specificity for tyrosine phosphorylation activity. A second high resolution motif representing CK2K198R substrate specificity was also generated. Here we report for the first time the impact of the OCNDS associated CK2K198R mutation. Contrary to prior speculation, the mutation does not result in a loss of function, but rather shifts the substrate specificity of the kinase. Broadly speaking the mutation leads to 1) a decreased preference for acidic residues in the +1 position, 2) a decreased preference for threonine phosphorylation, 3) an increased preference for tyrosine phosphorylation, and 4) an alteration of the tyrosine phosphorylation specificity motif. To further investigate the result of this mutation we have developed a probability-based scoring method, allowing us to predict shifts in phosphorylation in the K198R mutant relative to the wild type kinase. As an initial step we have applied the methodology to the set of axonally localized ion channels in an effort to uncover potential alterations of the phosphoproteome associated with the OCNDS disease condition.

Objectives. To explore the safety and efficacy profile of teriflunomide in progressive multiple sclerosis. Methods. We conducted a single-center retrospective observational analysis of a progressive multiple sclerosis population, assessing safety and efficacy in patients treated at least one year with teriflunomide or glatiramer acetate. Sustained progression of expanded disability status scale and sustained worsening of timed 25-foot walk were compared using a Cox proportional hazards model. Results. Teriflunomide group ( n = 29 ) mean characteristics: age = 58 years ( SD ± 7.6 ), disease   duration = 16.7 years ( SD ± 9.5 ), expanded   disability   status   score = 5.9 ( SD ± 1.3 ), and follow − up = 32.4 months ( SD ± 13.6 ). Glatiramer acetate group ( n = 30 ) mean characteristics: age = 52.4 years ( SD ± 11.3 ), disease   duration = 15.1 years ( SD ± 10.4 ), expanded   disability   status   score = 5.7 ( SD ± 1.6 ), and follow − up = 46.9 months ( SD ± 43.9 ). Both treatments were well tolerated without serious side effects. After adjustment for age, sex, and baseline expanded disability status score, sustained expanded disability status score progression did not differ between groups ( hazard   ratio = 1.17 ; 95% confidence interval: 0.45, 3.08; p = 0.75 ). Sustained timed 25-foot walk worsening after adjustment also did not differ ( hazard   ratio = 0.56 ; 95% confidence interval: 0.2, 1.53; p = 0.26 ). Conclusion. In an advanced progressive multiple sclerosis population, no substantial differences in tolerability, safety, sustained EDSS progression, or sustained T25FW worsening over time were observed between glatiramer acetate and teriflunomide-treated groups. The small sample precluded definitive determination.