Abstract
BACKGROUND: Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA).
METHODS: We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy.
RESULTS: De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases.
CONCLUSION: Our results expand the clinical and mutational spectrum of CACNA1A-related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.
| Original language | English |
|---|---|
| Journal | European Journal of Paediatric Neurology |
| DOIs | |
| Publication status | E-pub ahead of print - Nov 30 2016 |
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Keywords
- Journal Article
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Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia. / Travaglini, Lorena; Nardella, Marta; Bellacchio, Emanuele; D'Amico, Adele; Capuano, Alessandro; Frusciante, Roberto; Di Capua, Matteo; Cusmai, Raffaella; Barresi, Sabina; Morlino, Silvia; Fernández, Mario José Sánchez; Trivisano, Marina; Specchio, Nicola; Valeriani, Massimiliano; Vigevano, Federico; Bertini, Enrico; Zanni, Ginevra.
In: European Journal of Paediatric Neurology, 30.11.2016.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia
AU - Travaglini, Lorena
AU - Nardella, Marta
AU - Bellacchio, Emanuele
AU - D'Amico, Adele
AU - Capuano, Alessandro
AU - Frusciante, Roberto
AU - Di Capua, Matteo
AU - Cusmai, Raffaella
AU - Barresi, Sabina
AU - Morlino, Silvia
AU - Fernández, Mario José Sánchez
AU - Trivisano, Marina
AU - Specchio, Nicola
AU - Valeriani, Massimiliano
AU - Vigevano, Federico
AU - Bertini, Enrico
AU - Zanni, Ginevra
N1 - Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
PY - 2016/11/30
Y1 - 2016/11/30
N2 - BACKGROUND: Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA).METHODS: We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy.RESULTS: De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases.CONCLUSION: Our results expand the clinical and mutational spectrum of CACNA1A-related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.
AB - BACKGROUND: Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA).METHODS: We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy.RESULTS: De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases.CONCLUSION: Our results expand the clinical and mutational spectrum of CACNA1A-related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.
KW - Journal Article
U2 - 10.1016/j.ejpn.2016.11.005
DO - 10.1016/j.ejpn.2016.11.005
M3 - Article
C2 - 28007337
JO - European Journal of Paediatric Neurology
JF - European Journal of Paediatric Neurology
SN - 1090-3798
ER -