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Newly characterised 5' and 3' regions of CACNA1A gene harbour mutations associated with Familial Hemiplegic Migraine and Episodic Ataxia
- Source :
- Journal of the neurological sciences (2008)., info:cnr-pdr/source/autori:Veneziano L, Guida S, Mantuano E, Bernard P, Tarantino P, Boccone L, Hisama FM, Carrera P, Jodice C, Frontali M./titolo:Newly characterised 5' and 3' regions of CACNA1A gene harbour mutations associated with Familial Hemiplegic Migraine and Episodic Ataxia./doi:/rivista:Journal of the neurological sciences/anno:2008/pagina_da:/pagina_a:/intervallo_pagine:/volume, Journal of the neurological sciences 276 (2009): 31–37. doi:10.1016/j.jns.2008.08.030, info:cnr-pdr/source/autori:Veneziano L, Guida S, Mantuano E, Bernard P, Tarantino P, Boccone L, Hisama FM, Carrera P, Jodice C, Frontali M./titolo:Newly characterised 5' and 3' regions of CACNA1A gene harbour mutations associated with Familial Hemiplegic Migraine and Episodic Ataxia./doi:10.1016%2Fj.jns.2008.08.030/rivista:Journal of the neurological sciences/anno:2009/pagina_da:31/pagina_a:37/intervallo_pagine:31–37/volume:276
- Publication Year :
- 2007
-
Abstract
- The CACNA1A gene codes for the alpha(1A) pore-forming subunit of Ca(2+) voltage-gated Cav2.1 channels. CACNA1A mutations are responsible for Familial Hemiplegic Migraine (FHM) type 1, Episodic Ataxia (EA) type 2 and Spinocerebellar Ataxia type 6. The structure of the human gene includes, at present, 49 exons; however almost nothing is known about the 5' regulatory region, and there is now evidence suggesting the presence of additional exons at the 3' of the gene. The 892 bp fragment upstream of exon 1 and its deletion mutants were characterised for their transcriptional activity by using luciferase as a reporter gene. The 3' region was analysed by Rapid Amplification of the cDNA 3' End. Both regions were screened for mutations in a series of FHM and EA patients by SSCP and sequencing. At the 5' end of the gene a minimal promoter region was identified within the first 497 bp from ATG. By screening a larger fragment for mutations, the 5 bp deletion (g.-757_-753delCTTTC) was identified in a FHM patient. The deletion significantly increased the transcriptional activity, most likely due to the removal of half a turn of the DNA helix, changing the orientation of downstream binding sites for transcriptional factors. At the 3' end of the gene a new exon 48, followed by a strong poly-A signal, was identified as well as a new splice variant. The 5 bp insertion (g.38429_38430insCTTTT) in this exon was found in an EA patient. The two new regions can open the way for the study of human CACNA1A gene expression regulation and can be sites of mutations associated with FHM or EA phenotypes.
- Subjects :
- DNA Mutational Analysis
Migraine with Aura
Molecular Sequence Data
Biology
medicine.disease_cause
Cell Line
Exon
Neuroblastoma
Cell Line, Tumor
medicine
Spinocerebellar ataxia type 6
Humans
Analysis of Variance
Computational Biology
Calcium Channels
Italy
Phenotype
Sequence Deletion
Ataxia
Exons
Gene
Familial hemiplegic migraine
Episodic ataxia
Genetics
Mutation
Tumor
Alternative splicing
medicine.disease
Settore BIO/18 - Genetica
Neurology
Spinocerebellar ataxia
Neurology (clinical)
Subjects
Details
- ISSN :
- 0022510X
- Volume :
- 276
- Issue :
- 1-2
- Database :
- OpenAIRE
- Journal :
- Journal of the neurological sciences
- Accession number :
- edsair.doi.dedup.....21d8cbfd4bd2568b249b5ca21862af85