Rare CACNA1A mutations leading to congenital ataxia
Abstract Human mutations in the CACNA1A gene that encodes the pore-forming $ α_{1A} $ subunit of the voltage-gated $ Ca_{V} $2.1 (P/Q-type) $ Ca^{2+} $ channel cause multiple neurological disorders including sporadic and familial hemiplegic migraine, as well as cerebellar pathologies such as episodic ataxia, progressive ataxia, and early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years. Such a pathological role is in accordance with the physiological relevance of $ Ca_{V} $2.1 in neuronal tissue, especially in the cerebellum. This review deals with the report of the main clinical features defining CA, along with the presentation of an increasing number of CACNA1A genetic variants linked to this severe cerebellar disorder in the context of $ Ca^{2+} $ homeostasis alteration. Moreover, the review describes each pathological mutation according to structural location and known molecular and cellular functional effects in both heterologous expression systems and animal models. In view of this information in correlation with the clinical phenotype, we take into consideration different pathomechanisms underlying the observed motor dysfunction in CA patients carrying CACNA1A mutations. Present therapeutic management in CA and options for the development of future personalized treatment based on $ Ca_{V} $2.1 dysfunction are also discussed..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:472 |
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| Enthalten in: |
Pflügers Archiv - 472(2020), 7 vom: 26. Mai, Seite 791-809 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Izquierdo-Serra, Mercè [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
2.1 (P/Q-type) voltage-dependent calcium channel |
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| Anmerkungen: |
© Springer-Verlag GmbH Germany, part of Springer Nature 2020 |
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| doi: |
10.1007/s00424-020-02396-z |
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| PPN (Katalog-ID): |
OLC2118311850 |
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| 520 | |a Abstract Human mutations in the CACNA1A gene that encodes the pore-forming $ α_{1A} $ subunit of the voltage-gated $ Ca_{V} $2.1 (P/Q-type) $ Ca^{2+} $ channel cause multiple neurological disorders including sporadic and familial hemiplegic migraine, as well as cerebellar pathologies such as episodic ataxia, progressive ataxia, and early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years. Such a pathological role is in accordance with the physiological relevance of $ Ca_{V} $2.1 in neuronal tissue, especially in the cerebellum. This review deals with the report of the main clinical features defining CA, along with the presentation of an increasing number of CACNA1A genetic variants linked to this severe cerebellar disorder in the context of $ Ca^{2+} $ homeostasis alteration. Moreover, the review describes each pathological mutation according to structural location and known molecular and cellular functional effects in both heterologous expression systems and animal models. In view of this information in correlation with the clinical phenotype, we take into consideration different pathomechanisms underlying the observed motor dysfunction in CA patients carrying CACNA1A mutations. Present therapeutic management in CA and options for the development of future personalized treatment based on $ Ca_{V} $2.1 dysfunction are also discussed. | ||
| 650 | 4 | |a Congenital ataxia | |
| 650 | 4 | |a Cerebellar atrophy | |
| 650 | 4 | |a Permanent ataxia | |
| 650 | 4 | |a Early-onset cerebellar signs | |
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| 700 | 1 | |a Serrano, Mercedes |0 (orcid)0000-0002-2056-2428 |4 aut | |
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