دورية أكاديمية
Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2
| العنوان: | Complete loss of P/Q calcium channel activity caused by a CACNA1A missense mutation carried by patients with episodic ataxia type 2 |
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| المؤلفون: | Guida, S, Trettel, F, Pagnutti, S, Mantuano, E, Tottene, A, Veneziano, L, Fellin, T, Spadaro, M, Stauderman, K, Williams, M, Volsen, S, Ophoff, R, Frants, R, Frontali, M, Pietrobon, D., IODICE, CARLA |
| المساهمون: | Guida, S, Trettel, F, Pagnutti, S, Mantuano, E, Tottene, A, Veneziano, L, Fellin, T, Spadaro, M, Stauderman, K, Williams, M, Volsen, S, Ophoff, R, Frants, R, Iodice, C, Frontali, M, Pietrobon, D |
| بيانات النشر: | Cell Press US |
| سنة النشر: | 2001 |
| المجموعة: | Universitá degli Studi di Roma "Tor Vergata": ART - Archivio Istituzionale della Ricerca |
| مصطلحات موضوعية: | Chromosome Mapping, Male, Cerebellar Ataxia, Cell Line, Chromosomes, Human, Pair 19, Transfection, Female, Protein Subunit, Protein Structure, Secondary, Calcium Channel, Patch-Clamp Technique, Calcium Channels, P-Type, Models, Molecular, Mutation, Missense, Membrane Potential, Mutagenesis, Site-Directed, Molecular Sequence Data, Amino Acid Sequence, Pedigree, Q-Type, Settore BIO/18 - GENETICA |
| الوصف: | Familial hemiplegic migraine, episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 are allelic disorders of the CACNA1A gene (coding for the alpha(1A) subunit of P/Q calcium channels), usually associated with different types of mutations (missense, protein truncating, and expansion, respectively). However, the finding of expansion and missense mutations in patients with EA2 has blurred this genotype-phenotype correlation. We report the first functional analysis of a new missense mutation, associated with an EA2 phenotype-that is, T-->C transition of nt 4747 in exon 28, predicted to change a highly conserved phenylalanine residue to a serine at codon 1491, located in the putative transmembrane segment S6 of domain III. Patch-clamp recording in HEK 293 cells, coexpressing the mutagenized human alpha(1A-2) subunit, together with human beta(4) and alpha(2)delta subunits, showed that channel activity was completely abolished, although the mutated protein is expressed in the cell. These results indicate that a complete loss of P/Q channel function is the mechanism underlying EA2, whether due to truncating or to missense mutations. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/wos/WOS:000166994200019; volume:68; issue:3; firstpage:759; lastpage:764; journal:AMERICAN JOURNAL OF HUMAN GENETICS; http://hdl.handle.net/2108/46429Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0035089729; http://www.ncbi.nlm.nih.gov/pubmed/11179022Test |
| الإتاحة: | http://hdl.handle.net/2108/46429Test http://www.ncbi.nlm.nih.gov/pubmed/11179022Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.15FC206C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |