Topic: developmental and epileptic encephalopathies

Mutations in the GRIN2D gene, encoding one of the subunits of NMDA receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEE). The clinical presentation of DEE includes epilepsy, motor and cognitive deficits, developmental delay, and a high mortality rate. Grin2d mice carrying the pathogenic V667I variant recapitulate key phenotypes of the human disease.To explore the effect of the Grin2d mutation on neuronal and synaptic functions, we used acute cerebellum brain slices recorded from wild-type (WT) and Grin2d mice. We recorded neuronal activity from Purkinje neuro

Val667Ile is a de novo variant discovered in the GRIN2D gene found to be associated with Developmental and Epileptic Encephalopathies (DEEs). DEEs are a group of devastating disorders that involve global developmental delay and epileptic abnormalities. Patients with this variant exhibit a range of cognitive and motoric impairments, including intractable epilepsy, intellectual disabilities, motor deficits and premature death. The market lacks suitable treatments that alleviate these symptoms, and available therapy is focused solely on the epileptic phenotype. Our aim is to find a therapy that t

Kv7.2 and Kv7.3 are neuronal voltage-gated potassium channel subunits encoded by KCNQ2 and KCNQ3 genes, underlying the M-current, a slowly activating and non-inactivating current involved in neuronal excitability control. Kv7.2 mutations lead to neonatal-onset epilepsies including developmental and epileptic encephalopathies (DEE), characterized by seizures, electroencephalographic abnormalities, and developmental delay. When expressed in vitro, most Kv7.2 variants cause loss-of-function (LoF) effects. In this study, we aimed to functionally characterize a de novo KCNQ2 mutation in the pore of

The sodium (Na+)-leak channel (NALCN) maintains neuronal resting membrane potential by conducting a sodium leak current. Pathogenic mutations in the NALCN channelosome complex (NALCN-UNC80-UNC79) are linked to rare developmental and epileptic encephalopathies. However, despite the prevalence of cognitive deficits in NALCN-related disorders, the precise role of NALCN in brain development remains elusive. To address this gap, we investigated the contribution of Nalcn to cortical neural circuit formation using mouse models. Employing Nalcn-GFP reporter mice in conjunction with immunohistochemistr

Developmental and epileptic encephalopathies (DEE) are a spectrum of severe neurological disorders with poorly understood aetiologies, often involving metabolic dysfunctions. Biallelic recessive pathogenic variants in the Solute carrier family 13 member 5 gene (SLC13A5) gene cause a severe form of DEE, characterized by intractable neonatal seizures, developmental delay, and tooth hypoplasia. SLC13A5 encodes the sodium-dependent citrate transporter (NaCT) on the plasma membrane, expressed in brain and liver. Recent investigations highlighted the relevance of NaCT in citrate uptake, influencing