| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Institutes of Neurological Sciences (Drs. S. Battistini and Guazzi) and Nervous and Mental Disease (Drs. Rocchi, Giannini, and N. Battistini), University of Siena, Italy; the Clinical Molecular Biology Laboratory (Drs. Stenirri, Piatti, Ferrari, and Carrera), IRCCS H S. Raffaele, Milan, Italy; the Institute for Biomedical Advanced Technologies (Dr. Gelfi), CNR, Milan, Italy; and the Department of Agro-Industrial Biotechnology (Dr. Righetti), University of Verone, Italy.
Address correspondence and reprint requests to Dr. Stefania Battistini, Institute of Neurological Science, University of Siena, Viale Bracci 2, 53100 Siena, Italy; e-mail: battistinis{at}unisi.it
OBJECTIVE: To search for mutations in the calcium channel gene CACNA1A and to study the genotype–phenotype correlation in a family with a severe familial hemiplegic migraine (FHM) phenotype and a slowly progressive cerebellar ataxia.
BACKGROUND: CACNA1A gene mutations on chromosome 19 are involved in approximately 50% of FHM families. The association of FHM and cerebellar ataxia has been reported in a small number of FHM families, all linked to chromosome 19.
METHODS: The proband, in addition to typical hemiplegic migraine attacks, experienced severe episodes during which hemiplegia was associated with acutely altered consciousness and fever lasting several days. She, as well as her affected sister, developed a permanent, late-onset cerebellar ataxia and cerebellar atrophy evident on MRI. Linkage analysis was performed and the whole CACNA1A gene, 47 exon–intron boundaries, was analyzed by double gradient–denaturing gradient gel electrophoresis (DG-DGGE).
RESULTS: Genetic studies suggested linkage to chromosome 19p13, and DG-DGGE analysis detected a heteroduplex fragment in exon 13 of the CACNA1A gene. By direct sequencing, a G-to-A substitution resulting in an arginine to glutamine change at codon 583 in the second putative voltage sensor domain of the channel 
1A-subunit, was identified, possibly representing the disease-causing mutation. The proband and her affected sister were treated with acetazolamide, reporting freedom from new FHM attacks but no benefit in the progression of ataxia.
CONCLUSIONS: The combination of episodic dysfunction and permanent deficit could depend on the variety of functions of calcium channels and their distribution in the nervous system.
This article has been cited by other articles:
|
|
 |
|
  C. J. C. Weisz, R. S. Raike, L. E. Soria-Jasso, and E. J. Hess Potassium Channel Blockers Inhibit the Triggers of Attacks in the Calcium Channel Mouse Mutant tottering J. Neurosci., April 20, 2005; 25(16): 4141 - 4145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Mantuano, L Veneziano, M Spadaro, P Giunti, S Guida, M G Leggio, L Verriello, N Wood, C Jodice, and M Frontali Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Cav2.1 causing episodic ataxia 2 J. Med. Genet., June 1, 2004; 41(6): e82 - e82. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Jen, G. W. Kim, and R. W. Baloh Clinical spectrum of episodic ataxia type 2 Neurology, January 13, 2004; 62(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Koeppen Familial Hemiplegic Migraine Arch Neurol, May 1, 2003; 60(5): 663 - 664. [Full Text] [PDF]
|
|
|
|
|
|
E. E. Kors, J. Haan, N. J. Giffin, L. Pazdera, C. Schnittger, G. G. Lennox, G. M. Terwindt, F. L. M. J. Vermeulen, A. M. J. M. Van den Maagdenberg, R. R. Frants, et al. Expanding the Phenotypic Spectrum of the CACNA1A Gene T666M Mutation: A Description of 5 Families With Familial Hemiplegic Migraine Arch Neurol, May 1, 2003; 60(5): 684 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Alonso, J. Barros, A. Tuna, J. Coelho, J. Sequeiros, I. Silveira, and P. Coutinho Phenotypes of Spinocerebellar Ataxia Type 6 and Familial Hemiplegic Migraine Caused by a Unique CACNA1A Missense Mutation in Patients From a Large Family Arch Neurol, April 1, 2003; 60(4): 610 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Yu and S. H. Horowitz Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil Neurology, January 14, 2003; 60(1): 120 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Kullmann The neuronal channelopathies Brain, June 1, 2002; 125(6): 1177 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Terwindt, E. Kors, J. Haan, F. Vermeulen, A. van den Maagdenberg, R. Frants, M. Ferrari, and for the International Hemiplegic Migraine Research Mutation Analysis of the CACNA1A Calcium Channel Subunit Gene in 27 Patients With Sporadic Hemiplegic Migraine Arch Neurol, June 1, 2002; 59(6): 1016 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Takahashi, S Igarashi, T Kimura, I Hozumi, I Kawachi, O Onodera, H Takano, M Saito, and S Tsuji Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a T666M mutation in the CACNA1A gene J. Neurol. Neurosurg. Psychiatry, May 1, 2002; 72(5): 676 - 677. [Full Text] [PDF]
|
|
|
|
|
|
W. Yu and S. H. Horowitz Familial hemiplegic migraine and its abortive therapy with intravenous verapamil Neurology, November 13, 2001; 57(9): 1732 - 1733. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Q. Gu, H. Yao, and G. G. Haddad Increased neuronal excitability and seizures in the Na+/H+ exchanger null mutant mouse Am J Physiol Cell Physiol, August 1, 2001; 281(2): C496 - C503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ducros, C. Denier, A. Joutel, M. Cecillon, C. Lescoat, K. Vahedi, F. Darcel, E. Vicaut, M.-G. Bousser, and E. Tournier-Lasserve The Clinical Spectrum of Familial Hemiplegic Migraine Associated with Mutations in a Neuronal Calcium Channel N. Engl. J. Med., July 5, 2001; 345(1): 17 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K A SCOGGAN, T CHANDRA, R NELSON, A F HAHN, and D E BULMAN Identification of two novel mutations in the CACNA1A gene responsible for episodic ataxia type 2 J. Med. Genet., April 1, 2001; 38(4): 249 - 253. [Full Text]
|
|
|
|
|
|
C. Denier, A. Ducros, A. Durr, B. Eymard, B. Chassande, and E. Tournier-Lasserve Missense CACNA1A Mutation Causing Episodic Ataxia Type 2 Arch Neurol, February 1, 2001; 58(2): 292 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Kraus, M. J. Sinnegger, A. Koschak, H. Glossmann, S. Stenirri, P. Carrera, and J. Striessnig Three New Familial Hemiplegic Migraine Mutants Affect P/Q-type Ca2+ Channel Kinetics J. Biol. Chem., March 24, 2000; 275(13): 9239 - 9243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Bennett Anchors Aweigh! : Ion Channels, Cytoskeletal Proteins, and Cellular Excitability Circ. Res., March 3, 2000; 86(4): 367 - 368. [Full Text] [PDF]
|
|
|
|
|
|
E. Tournier-Lasserve CACNA1A mutations Neurology, July 1, 1999; 53(1): 3 - 3. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
