Bi-allelic loss-of-function CACNA1B mutations in progressive epilepsy-dyskinesia

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment

Race and Romance: Coloring the Past

Race and Romance: Coloring the Past explores the literary and cultural genealogy of colorism, white passing, and white presenting in the romance genre. The scope of the study ranges from Heliodorus’ Aithiopika to the short novels of Aphra Behn, to the modern romance novel Forbidden by Beverly Jenkins. This analysis engages with the troublesome racecraft of “passing” and the instability of racial identity and its formation from the premodern to the present. The study also looks at the significance of white settler colonialism to early modern romance narratives. A bridge between studies of early modern romance and scholarship on twenty-first-century romance novels, this book is well-suited for those interested in the romance genre.</jats:p