The Spectrum of DEPDC5-Related Epilepsy
| Autor: | Elena R. Praticò, Giulia Salomone, Manuela Lo Bianco, Giulia Pecora, Mattia Comella, Anna Portale, Giuseppe Costanza, Sarah Sciuto, Raffaele Falsaperla |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MTORopathies Pediatrics medicine.medical_specialty DEPDC5 Agonists of GATOR1 business.industry MTORC1 inhibitors GATOR1 Focal epilepsy medicine.disease Focal cortical dysplasia MTORC1 pathway 03 medical and health sciences Epilepsy 030104 developmental biology 0302 clinical medicine Epilepsy surgery Pediatrics Perinatology and Child Health Medicine Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Pediatric Neurology. |
| ISSN: | 1875-9041 1304-2580 |
| DOI: | 10.1055/s-0041-1727139 |
| Popis: | Disheveled EGL-10 and pleckstrin domain-containing protein 5 (DEPDC5) is a key member of the GAP activity toward rags complex 1 complex, which inhibits the mammalian target of rapamycin complex 1 (mTORC1) pathway. DEPDC5 loss-of-function mutations lead to an aberrant activation of the mTOR signaling. At neuronal level, the increased mTOR cascade causes the generation of epileptogenic dysplastic neuronal circuits and it is often associated with malformation of cortical development. The DEPDC5 phenotypic spectrum ranges from sporadic early-onset epilepsies with poor neurodevelopmental outcomes to familial focal epilepsies and sudden unexpected death in epilepsy; a high rate of inter- and intrafamilial variability has been reported. To date, clear genotype–phenotype correlations have not been proven. More studies are required to elucidate the significance of likely pathogenic/variants of uncertain significance. The pursuit of a molecular targeted antiepileptic therapy is a future challenge. |
| Databáze: | OpenAIRE |
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