Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinica...

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Detalles Bibliográficos
Autores: Carreño, Oriel, Corominas, Roser, Serra Pascual, Selma A., 1981-, Sintas, Cèlia, Fernández Castillo, Noelia, Vila Pueyo, Marta, Toma, Claudio, Gené, Gemma, Pons, Roser, Llaneza, Miguel, Sobrido, María Jesús, Grinberg, Daniel, Valverde, M. A. (Miguel Ángel), 1963-, Fernández-Fernández, José Manuel, 1967-, Macaya, Alfons, Cormand, Bru
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/25626
Acceso en línea:http://hdl.handle.net/10230/25626
http://dx.doi.org/10.1002/mgg3.24
Access Level:acceso abierto
Palabra clave:Migranya -- Aspectes genètics
ATP1A2
CACNA1A
Functional studies
Hemiplegic migraine
Mutation analysis
Descripción
Sumario:Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing.

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