Anti-CSNK2B monoclonal antibody, clone 7G8

CSNK2B, which encodes the beta subunit of casein kinase II (CK2), plays an important role in neuron morphology and synaptic transmission. Variants in CSNK2B associated with epilepsy and/or intellectual disability (ID)/developmental delay (DD) have been reported in five cases only. Among the 816 probands suspected hereditary epilepsy whose initial report of trio-based whole exome sequencing (WES) were negative, 10 de novo pathogenic or likely pathogenic variants of CSNK2B in nine probands were identified after reanalysis of their raw Trio-WES data. Six of the nine epileptic patients had ID/ DD. The age of seizure onset of these nine patients with CSNK2B variants ranged from 2-12 months. Eight patients had age of seizure onset of less than 6 months. The epilepsy of most probands (8/9) was generalized tonic-clonic seizure and clustered (6/9). Most patients had normal electroencephalogram (5/9) and brain magnetic resonance image (7/9) results. Most patients (7/9) had easy-to-control seizures. Levetiracetam was the most commonly used drug in seizure-free patients (5/7). The variants detected in five patients (5/9, 55.6%) were located in the zinc-binding domain. In summary, our research provided evidence that variants in CSNK2B are associated with epilepsy with or without ID/DD. CSNK2B-related epilepsy is relatively easy to be controlled. The zinc-binding domain appears to be the hotspot region for mutation.

Uterine leiomyomas are benign tumors affecting a large proportion of the female population. Despite the very high prevalence, the molecular basis for understanding the onset and development of the disease are still poorly understood. In this study, we profiled the proteomes and kinomes of leiomyoma as well as myometrium samples from patients to a depth of >7000 proteins including 200 kinases. Statistical analysis identified a number of molecular signatures distinguishing healthy from diseased tissue. Among these, nine kinases (ADCK4, CDK5, CSNK2B, DDR1, EPHB1, MAP2K2, PRKCB, PRKG1, and RPS6KA5) representing a number of cellular signaling pathways showed particularly strong discrimination potential. Preliminary statistical analysis by receiver operator characteristics plots revealed very good performance for individual kinases (area under the curve, AUC of 0.70-0.94) as well as binary combinations thereof (AUC 0.70-1.00) that might be used to assess the activity of signaling pathways in myomas. Of note, the receptor tyrosine kinase DDR1 holds future potential as a drug target owing to its strong links to collagen signaling and the excessive formation of extracellular matrix typical for leiomyomas in humans.