Calcium Channels Genes and Their Epilepsy Phenotypes
| Autor: | Giulio Pulvirenti, Marina Mazzurco, Martina Caccamo, Manuela Lo Bianco, Gloria Gangi, Raffaele Falsaperla, Antonio Zanghì, Alessandro Giallongo, Elena R. Praticò |
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| Rok vydání: | 2021 |
| Předmět: |
Genetics
biology Voltage-dependent calcium channel business.industry Calcium channel Gene mutation medicine.disease Epilepsy Childhood absence epilepsy Pediatrics Perinatology and Child Health Epilepsy syndromes CACNA1H biology.protein medicine Spinocerebellar ataxia type 6 Neurology (clinical) business |
| Zdroj: | Journal of Pediatric Neurology. 21:224-234 |
| ISSN: | 1875-9041 1304-2580 |
| DOI: | 10.1055/s-0041-1728684 |
| Popis: | Calcium (Ca2+) channel gene mutations play an important role in the pathogenesis of neurological episodic disorders like epilepsy. CACNA1A and CACNA1H genes are involved in the synthesis of calcium channels. Mutations in the α1A subunit of the P/Q type voltage-gated calcium channel gene (CACNA1A) located in 19p13.13, which encodes for the transmembrane pore-forming subunit of CAV2.1 voltage-dependent calcium channel, have been correlated to a large clinical spectrum of epilepsy such as idiopathic genetic epilepsy, early infantile epilepsy, and febrile seizures. Moreover, CACNA1A mutations have been demonstrated to be involved in spinocerebellar ataxia type 6, familiar hemiplegic migraine, episodic ataxia type 2, early-onset encephalopathy, and hemiconvulsion–hemiplegia epilepsy syndrome. This wide phenotype heterogeneity associated with CACNA1A mutations is correlated to different clinical and electrophysiological manifestations. CACNA1H gene, located in 16p13.3, encodes the α1H subunit of T-type calcium channel, expressing the transmembrane pore-forming subunit Cav3.2. Despite data still remain controversial, it has been identified as an important gene whose mutations seem strictly related to the pathogenesis of childhood absence epilepsy and other generalized epilepsies. The studied variants are mainly gain-of-function, hence responsible for an increase in neuronal susceptibility to seizures. CACNA1H mutations have also been associated with autism spectrum disorder and other behavior disorders. More recently, also amyotrophic lateral sclerosis has been related to CACNA1H alterations. The aim of this review, other than describe the CACNA1A and CACNA1H gene functions, is to identify mutations reported in literature and to analyze their possible correlations with specific epileptic disorders, purposing to guide an appropriate medical treatment recommendation. |
| Databáze: | OpenAIRE |
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