Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia

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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 languageEnglish
JournalEuropean Journal of Paediatric Neurology
DOIs
Publication statusE-pub ahead of print - Nov 30 2016

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Missense Mutation
Ataxia
Migraine Disorders
Cerebellar Diseases
Mutation
Presynaptic Terminals
Nervous System Diseases
Genes
Atrophy
Seizures
Phenotype
Neurons
Brain

Keywords

  • Journal Article

Cite this

@article{8858badfb06e43b48155ea3cf3a3d053,
title = "Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia",
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.",
keywords = "Journal Article",
author = "Lorena Travaglini and Marta Nardella and Emanuele Bellacchio and Adele D'Amico and Alessandro Capuano and Roberto Frusciante and {Di Capua}, Matteo and Raffaella Cusmai and Sabina Barresi and Silvia Morlino and Fern{\'a}ndez, {Mario Jos{\'e} S{\'a}nchez} and Marina Trivisano and Nicola Specchio and Massimiliano Valeriani and Federico Vigevano and Enrico Bertini and Ginevra Zanni",
note = "Copyright {\circledC} 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.",
year = "2016",
month = "11",
day = "30",
doi = "10.1016/j.ejpn.2016.11.005",
language = "English",
journal = "European Journal of Paediatric Neurology",
issn = "1090-3798",
publisher = "W.B. Saunders Ltd",

}

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 -