The p.Glu787Lys variant in the GRIA3 gene causes developmental and epileptic encephalopathy mimicking structural epilepsy in a female patient.

The GRIA3 gene is located in the X chromosome and encodes for one of the subunits (iGluR3) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), an excitatory synaptic transmission receptor present in most parts of the brain. iGluR3 dysfunction has been associated with both abnormal memory formation and learning. It has been observed in patients with different neurological and cognitive disorders, including epilepsy. Three different de novo missense variants of GRIA3 have recently been reported in patients with Developmental and Epileptic Encephalopathy (DEE). We report on a female pediatric patient with DEE whose clinical picture mimicked structural epilepsy. We give a detailed description of our patient's most important electro-clinical features. Genetic analysis revealed that the patient carried a de novo missense variant in GRIA3 (c.2359G>A; p.Glu787Lys). The p.Glu787Lys variant had previously been reported in a male pediatric patient. Additionally, we studied iGluR3 expression in the patient and control fibroblasts. We found significantly lower iGluR3 expression in the patient's fibroblasts than in controls and different responses to glutamate treatment. In summary, our report expands knowledge of GRIA3 variants affecting boys and girls, describes functional studies of these variants, and provides an extensive review of the literature concerning GRIA3 genetic variants.

Epilepsy in LAMA2-related muscular dystrophy: An electro-clinico-radiological characterization.

OBJECTIVE: To delineate the epileptic phenotype of LAMA2-related muscular dystrophy (MD) and correlate it with the neuroradiological and muscle biopsy findings, as well as the functional motor phenotype. METHODS: Clinical, electrophysiological, neuroradiological, and histopathological data of 25 patients with diagnosis of LAMA2-related MD were analyzed. RESULTS: Epilepsy occurred in 36% of patients with LAMA2-related MD. Mean age at first seizure was 8 years. The most common presenting seizure type was focal-onset seizures with or without impaired awareness. Visual aura and autonomic signs, including vomiting, were frequently reported. Despite a certain degree of variability, bilateral occipital or temporo-occipital epileptiform abnormalities were by far the most commonly observed. Refractory epilepsy was found in 75% of these patients. Epilepsy in LAMA2-related MD was significantly more prevalent in those patients in whom the cortical malformations were more extensive. In contrast, the occurrence of epilepsy was not found to be associated with the patients' motor ability, the size of their white matter abnormalities, or the amount of residual merosin expressed on muscle. SIGNIFICANCE: The epileptic phenotype of LAMA2-related MD is characterized by focal seizures with prominent visual and autonomic features associated with EEG abnormalities that predominate in the posterior quadrants. A consistent correlation between epileptic phenotype and neuroimaging was identified, suggesting that the extension of the polymicrogyria may serve as a predictor of epilepsy occurrence.