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

Lorena Travaglini; Marta Nardella; Emanuele Bellacchio; Adele D'Amico; Alessandro Capuano; Roberto Frusciante; Matteo Di Capua; Raffaella Cusmai; Sabina Barresi; Silvia Morlino; Mario José Sánchez Fernández; Marina Trivisano; Nicola Specchio; Massimiliano Valeriani; Federico Vigevano; Enrico Bertini; Ginevra Zanni

doi:10.1016/j.ejpn.2016.11.005

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

Lorena Travaglini, Marta Nardella, Emanuele Bellacchio, Adele D'Amico, Alessandro Capuano, Roberto Frusciante, Matteo Di Capua, Raffaella Cusmai, Sabina Barresi, Silvia Morlino, Mario José Sánchez Fernández, Marina Trivisano, Nicola Specchio, Massimiliano Valeriani, Federico Vigevano, Enrico Bertini, Ginevra Zanni

Ospedale Pediatrico Bambino Gesu

Research output: Contribution to journal › Article › peer-review

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	https://doi.org/10.1016/j.ejpn.2016.11.005
Publication status	E-pub ahead of print - Nov 30 2016

Keywords

Journal Article

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Travaglini, L., Nardella, M., Bellacchio, E., D'Amico, A., Capuano, A., Frusciante, R., Di Capua, M., Cusmai, R., Barresi, S., Morlino, S., Fernández, M. J. S., Trivisano, M., Specchio, N., Valeriani, M., Vigevano, F., Bertini, E., & Zanni, G. (2016). Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia. European Journal of Paediatric Neurology. https://doi.org/10.1016/j.ejpn.2016.11.005

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 › peer-review

Travaglini, L, Nardella, M, Bellacchio, E , D'Amico, A , Capuano, A, Frusciante, R, Di Capua, M , Cusmai, R, Barresi, S, Morlino, S, Fernández, MJS, Trivisano, M , Specchio, N , Valeriani, M , Vigevano, F , Bertini, E & Zanni, G 2016, 'Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia', European Journal of Paediatric Neurology. https://doi.org/10.1016/j.ejpn.2016.11.005

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. / Missense mutations of CACNA1A are a frequent cause of autosomal dominant nonprogressive congenital ataxia. In: European Journal of Paediatric Neurology. 2016.

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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.",

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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

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.

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