Migraine, familial hemiplegic, 1; FHM1
GtoPdb Disease Summaries
This section gives an overview of the disease, and where available shows the following:
- Synonyms: Shows known synonyms for the disease.
- Description: Gives a basic description/definition of the disease.
- Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
- Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
- Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.
More information can be found in the help pages.
✖| Disease ID: | 627 | |
| Name: | Migraine, familial hemiplegic, 1; FHM1 | |
| Associated with: | 1 target | |
| Synonyms |
| Familial hemiplegic migraine | Familial or sporadic hemiplegic migraine |
| Database Links |
|
Disease Ontology:
DOID:0060178 OMIM: 141500 Orphanet: ORPHA569 |
Targets
GtoPdb Disease Summaries - Targets
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Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.
If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page
Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.
More information can be found in the help pages.
✖| Cav2.1 | |
| Comments: | The majority of FHM-1 mutations are located in the S4 voltage sensors and flanking regions. Examination of FHM-1 mutations on Cav2.1 biophysical properties using electrophysiological analysis in Xenopus laevis oocytes and HEK-293 cells shows considerable variability that may be accounted for by the use of different expression systems, Cav2.1 splice variants, auxiliary subunits and experimental conditions. Overall trends point towards FHM-1 mutations causing a predicted gain-of-function phenotype: shift of V0.5,act to more hyperpolarised potentials, increased availability of opening at lower membrane potentials, increased channel open probability and single channel conductance. Knock-in mice carrying R192Q and S218L FHM-1 mutations support gain-of-function in showing a lower threshold for stimulation of cortical spreading depression and increased velocity of propagation across the cortex, increased presynaptic basal calcium levels and altered synaptic plasticity. The severity of phenotype resulting from some FHM-1 mutations appears to be affected by CACNA1A alternative splicing. |
| References: | 1-3 |
| Mutations: | Cav2.1 is associated with 18 mutation. Click here for details  |
Ligands
GtoPdb Disease Summaries - Ligands
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- Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
- Immuno: Immuno icon indicates the ligand is immuno-relevant
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- Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
- Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
- Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.
More information can be found in the help pages.
✖No ligand related data available for Migraine, familial hemiplegic, 1; FHM1
References
1. Adams PJ, Garcia E, David LS, Mulatz KJ, Spacey SD, Snutch TP. (2009) Ca(V)2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: implications for calcium channelopathies. Channels (Austin), 3 (2): 110-21. [PMID:19242091]
2. Adams PJ, Rungta RL, Garcia E, van den Maagdenberg AM, MacVicar BA, Snutch TP. (2010) Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel. Proc Natl Acad Sci USA, 107 (43): 18694-9. [PMID:20937883]
3. Adams PJ, Snutch TP. (2007) Calcium channelopathies: voltage-gated calcium channels. Subcell Biochem, 45: 215-51. [PMID:18193639]
4. Barrett CF, Cao YQ, Tsien RW. (2005) Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type calcium channel. J Biol Chem, 280 (25): 24064-71. [PMID:15795222]
5. Cao YQ, Tsien RW. (2005) Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. Proc Natl Acad Sci USA, 102 (7): 2590-5. [PMID:15699344]
6. Carrera P, Piatti M, Stenirri S, Grimaldi LM, Marchioni E, Curcio M, Righetti PG, Ferrari M, Gelfi C. (1999) Genetic heterogeneity in Italian families with familial hemiplegic migraine. Neurology, 53 (1): 26-33. [PMID:10408532]
7. Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, Darcel F, Vicaut E, Bousser MG, Tournier-Lasserve E. (2001) The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med, 345 (1): 17-24. [PMID:11439943]
8. Ducros A, Denier C, Joutel A, Vahedi K, Michel A, Darcel F, Madigand M, Guerouaou D, Tison F, Julien J et al.. (1999) Recurrence of the T666M calcium channel CACNA1A gene mutation in familial hemiplegic migraine with progressive cerebellar ataxia. Am J Hum Genet, 64 (1): 89-98. [PMID:9915947]
9. Gardner K, BernalO, Keegan M, Badger J, Gerber O, Lowry N, Hoffman EP. (1999) A new mutation in the Chr19p calcium channel gene CACNLIA4 causing hemiplegic migraine with ataxia. Neurology, 52 (suppl. 2): A115.
10. Hans M, Luvisetto S, Williams ME, Spagnolo M, Urrutia A, Tottene A, Brust PF, Johnson EC, Harpold MM, Stauderman KA et al.. (1999) Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. J Neurosci, 19 (5): 1610-9. [PMID:10024348]
11. Kaja S, van de Ven RC, Broos LA, Veldman H, van Dijk JG, Verschuuren JJ, Frants RR, Ferrari MD, van den Maagdenberg AM, Plomp JJ. (2005) Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness. Neuroscience, 135 (1): 81-95. [PMID:16111830]
12. Kors EE, Haan J, Giffin NJ, Pazdera L, Schnittger C, Lennox GG, Terwindt GM, Vermeulen FL, Van den Maagdenberg AM, Frants RR et al.. (2003) Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine. Arch Neurol, 60 (5): 684-8. [PMID:12756131]
13. Kors EE, Melberg A, Vanmolkot KR, Kumlien E, Haan J, Raininko R, Flink R, Ginjaar HB, Frants RR, Ferrari MD et al.. (2004) Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation. Neurology, 63 (6): 1136-7. [PMID:15452324]
14. Kors EE, Terwindt GM, Vermeulen FL, Fitzsimons RB, Jardine PE, Heywood P, Love S, van den Maagdenberg AM, Haan J, Frants RR et al.. (2001) Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol, 49 (6): 753-60. [PMID:11409427]
15. Kraus RL, Sinnegger MJ, Glossmann H, Hering S, Striessnig J. (1998) Familial hemiplegic migraine mutations change alpha1A Ca2+ channel kinetics. J Biol Chem, 273 (10): 5586-90. [PMID:9488686]
16. Kraus RL, Sinnegger MJ, Koschak A, Glossmann H, Stenirri S, Carrera P, Striessnig J. (2000) Three new familial hemiplegic migraine mutants affect P/Q-type Ca(2+) channel kinetics. J Biol Chem, 275 (13): 9239-43. [PMID:10734061]
17. Melliti K, Grabner M, Seabrook GR. (2003) The familial hemiplegic migraine mutation R192Q reduces G-protein-mediated inhibition of P/Q-type (Ca(V)2.1) calcium channels expressed in human embryonic kidney cells. J Physiol (Lond.), 546 (Pt 2): 337-47. [PMID:12527722]
18. Müllner C, Broos LA, van den Maagdenberg AM, Striessnig J. (2004) Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects. J Biol Chem, 279 (50): 51844-50. [PMID:15448138]
19. Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M et al.. (1996) Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell, 87 (3): 543-52. [PMID:8898206]
20. Romaniello R, Zucca C, Tonelli A, Bonato S, Baschirotto C, Zanotta N, Epifanio R, Righini A, Bresolin N, Bassi MT et al.. (2010) A wide spectrum of clinical, neurophysiological and neuroradiological abnormalities in a family with a novel CACNA1A mutation. J Neurol Neurosurg Psychiatr, 81 (8): 840-3. [PMID:20682717]
21. Stam AH, Vanmolkot KR, Kremer HP, Gärtner J, Brown J, Leshinsky-Silver E, Gilad R, Kors EE, Frankhuizen WS, Ginjaar HB et al.. (2008) CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine. Clin Genet, 74 (5): 481-5. [PMID:18400034]
22. Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, Pietrobon D. (2002) Familial hemiplegic migraine mutations increase Ca(2+) influx through single human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons. Proc Natl Acad Sci USA, 99 (20): 13284-9. [PMID:12235360]
23. Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AM, Pietrobon D. (2005) Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. J Biol Chem, 280 (18): 17678-86. [PMID:15743764]
24. Vahedi K, Denier C, Ducros A, Bousson V, Levy C, Chabriat H, Haguenau M, Tournier-Lasserve E, Bousser MG. (2000) CACNA1A gene de novo mutation causing hemiplegic migraine, coma, and cerebellar atrophy. Neurology, 55 (7): 1040-2. [PMID:11061267]
25. van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T, van de Ven RC, Tottene A, van der Kaa J, Plomp JJ et al.. (2004) A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron, 41 (5): 701-10. [PMID:15003170]
