NAPB and developmental and epileptic encephalopathy: description of the electro-clinical profile associated to a novel pathogenic variant.

Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. DEE are genetically heterogeneous and the proteins involved play role in multiple pathways such as synaptic transmission, metabolism, neuronal development or maturation, transcriptional regulation or intracellular trafficking. We performed whole exome sequencing in a consanguineous family with 3 children presenting an early-onset (< 6 months) with cluster of seizures characterized by oculomotor and vegetative manifestations, with an occipital origin. Before one year of age, interictal electroencephalographic recordings were well organized and neurodevelopment was unremarkable. Then, a severe regression occurred. We identified a novel homozygous protein-truncating variant in the NAPB (NSF attachment protein beta) gene that encodes the βSNAP protein, a key regulator of the NSF (N-ethylmaleimide-sensitive fusion) ATPase. This enzyme is essential for synaptic transmission by disassembling and recycling proteins of the SNARE complex. Here, we describe the electro-clinical profile of each patient during the disease course. Our findings strengthen the association between bi-allelic variants in NAPB and DEE and refine the associated phenotype. We suggest to include this gene in the targeted epilepsy gene panels used for routine diagnosis of unexplained epilepsy.