STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies
| Autor: | Noah Guy Lewis Guiberson, Debra Abramov, Jacqueline Burré |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Encephalopathy Context (language use) Bioinformatics Biochemistry Article Frameshift mutation 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Munc18 Proteins medicine STXBP1 Missense mutation Animals Humans Gene Brain Diseases business.industry Brain medicine.disease Phenotype 030104 developmental biology Neurodevelopmental Disorders Mutation Anticonvulsants business Haploinsufficiency 030217 neurology & neurosurgery |
| Zdroj: | J Neurochem |
| ISSN: | 1471-4159 |
| Popis: | Mutations in Munc18-1/STXBP1 (syntaxin-binding protein 1) are linked to various severe early epileptic encephalopathies and neurodevelopmental disorders. Heterozygous mutations in the STXBP1 gene include missense, nonsense, frameshift, and splice site mutations, as well as intragenic deletions and duplications and whole-gene deletions. No genotype-phenotype correlation has been identified so far, and patients are treated by anti-epileptic drugs because of the lack of a specific disease-modifying therapy. The molecular disease mechanisms underlying STXBP1-linked disorders are yet to be fully understood, but both haploinsufficiency and dominant-negative mechanisms have been proposed. This review focuses on the current understanding of the phenotypic spectrum of STXBP1-linked disorders, as well as discusses disease mechanisms in the context of the numerous pathways in which STXBP1 functions in the brain. We additionally evaluate the available animal models to study these disorders and highlight potential therapeutic approaches for treating these devastating diseases. |
| Databáze: | OpenAIRE |
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