Patients suffering from the rare hereditary disease hypophosphatasia (HPP), which is based on mutations in the ALPL gene, tend to develop central nervous system (CNS) related issues like epileptic seizures and neuropsychiatric illnesses such as anxiety and depression, in addition to well-known problems with the mineralization of bones and teeth.
Analyses of functional properties of four nAChR mutants associated with ADNFLE indicate that a gain of function of these mutant receptors may be at the origin of the neuronal network dysfunction that causes the epileptic seizures.
We report a case of a 10-month-old girl presented with reflex epileptic seizures provoked by somatosensory stimuli with a novel de novo mutation of SCN1A gene.
We previously reported predominant Nav1.1 expression in parvalbumin-expressing (PV+) inhibitory neurons in juvenile mouse brain and observed epileptic seizures in mice with selective deletion of Scn1a in PV+ cells mediated by PV-Cre transgene expression (Scn1a<sup>fl/+</sup>/PV-Cre-TG).
Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation.
In a multivariate analysis, high xCT expression and WHO tumor grade but not IDH1R132H mutation, were significantly associated with epileptic seizures at diagnosis (odds ratio 2.2, p = 0.02).
Our findings indicate that an abnormality in GluA1 palmitoylation can lead to hyperexcitability in the cerebrum, which negatively affects the maintenance of network stability, resulting in epileptic seizures.<b>SIGNIFICANCE STATEMENT</b> AMPARs predominantly mediate excitatory synaptic transmission.
Here we report an infant and his father with early onset focal epileptic seizures but without cognitive or neurological impairment in whom next generation sequence analysis identified a heterozygous mutation (c.5630A > G, p. (Asn1877Ser)) in the SCN8A gene.
Presenilin 1 (PSEN1) gene mutations deterministic for Alzheimer's disease (AD) are associated with marked heterogeneity in clinical phenotype, with behavioral and psychiatric features, parkinsonism, myoclonus, epileptic seizures, spastic paraparesis, frontal behavioral changes suggestive of the phenotype of frontotemporal dementia, aphasia, and cerebellar ataxia being described as well as cognitive decline.
Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum.
Recently, exonic microdeletions in the gephyrin (GPHN) gene have been associated with neurodevelopmental disorders including autism spectrum disorder, schizophrenia and epileptic seizures.
KCC3 mutations have been associated with hereditary motor and sensory polyneuropathy with corpus callosum agenesis (Andermann syndrome) that often manifests with epileptic seizures.
Angelman syndrome is characterised by neurodevelopmental impairment (with or without epileptic seizures) associated with functional deficit of the UBE3A gene.
Antibodies to the glutamate/AMPA receptor subunit 3 (GluR3), are found in a human epilepsy, Rasmussen's encephalitis [RE], and were hypothesized as the major cause for the neuronal loss, chronic inflammatory changes and epileptic seizures characteristic of the disease.