Migraine genetics: An update

Haan, Joost; Kors, Esther E.; Vanmolkot, Kaate R J; Maagdenberg, Arn M. J. M. van den; Frants, Rune R.; Ferrari, Michel

doi:10.1007/s11916-005-0065-9

Cited by 46 publications

(27 citation statements)

References 93 publications

(48 reference statements)

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“…Disorders not associated with FHM are episodic ataxia type 2 (Zafeiriou et al 2009, Cuenca-Leon et al 2009, Cricchi et al 2007, Jen et al 2004, 2008, Ophoff et al 1996, progressive ataxia (Yue et al 1997), spinocerebellar ataxia type 6 (Tsou et al , Restituito et al 2000, Ishikawa et al 1999, Zhuchenko et al 1997) and absence (Imbrici et al 2004) and generalized epilepsy (Haan et al 2005, Jouvenceau et al 2001). In addition FHM1 mutations were also found in family members who had only "normal" no-paretic migraine but no FHM.…”

Section: C2 Familial Hemiplegic Migraine Typementioning

confidence: 99%

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

Uchitel

Inchauspe

Urbano

et al. 2012

Journal of Physiology-Paris

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Section: C2 Familial Hemiplegic Migraine Typementioning

confidence: 99%

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

Uchitel

Inchauspe

Urbano

et al. 2012

Journal of Physiology-Paris

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“…1). Eighteen different missense mutations associated with FHM1 have been described, including the Y1385C SHM mutation 19,20 (FIG. 1).…”

Section: Familial Hemiplegic Migraine Type 1 (Fhm1)mentioning

confidence: 99%

“…FHM2 families often include affected individuals who have a history of seizures and, as with FHM1, some FHM2 patients experience severe episodic neurological deficits such as confusion or impaired consciousness, fever, delayed edema, and permanent mental retardation. 19 A missense mutation in the ATP1A2 gene (T378N) was also found in two (or one and the same?) families with features that bridge the clinical spectrum between FHM and alternating hemiplegia of childhood (AHC), a rare syndrome characterized by early onset of episodic hemiplegia or quadriplegia with autonomic disturbances, movement disorders, and progressive cognitive impairment.…”

Section: Figmentioning

confidence: 99%

Familial Hemiplegic Migraine

2007

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Summary: Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A and SCNA1A, encoding the pore-forming ␣ 1 subunits of the neuronal voltage-gated Ca 2ϩ channels Ca V 2.1 and Na ϩ channels Na V 1.1, are responsible for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the ␣ 2 subunit of the Na ϩ , K ϩ adenosinetriphosphatase (ATPase), are responsible for FHM2. This review discusses the functional studies of two FHM1 knockin mice and of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1 FHM3). These studies show the following: (1) FHM1 mutations produce gain-of-function of the Ca V 2.1 channel and, as a consequence, increased Ca V 2.1-dependent neurotransmitter release from cortical neurons and facilitation of in vivo induction and propagation of cortical spreading depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations produce loss-of-function of the ␣ 2 Na ϩ ,K ϩ -ATPase; and (3) the FHM3 mutation accelerates recovery from fast inactivation of Na V 1.5 (and presumably Na V 1.1) channels. These findings are consistent with the hypothesis that FHM mutations share the ability of rendering the brain more susceptible to CSD by causing either excessive synaptic glutamate release (FHM1) or decreased removal of K ϩ and glutamate from the synaptic cleft (FHM2) or excessive extracellular K ϩ (FHM3). The FHM data support a key role of CSD in migraine pathogenesis and point to cortical hyperexcitability as the basis for vulnerability to CSD and to migraine attacks. Hence, they support novel therapeutic strategies that consider CSD and cortical hyperexcitability as key targets for preventive migraine treatment.

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“…[18][19][20][21][22] These neurological disorders are dominantly inherited and caused primarily by missense mutations, which are thought to confer a mild hypomorphic loss-of-function. In the present study, the proband suffered from hearing loss and migraines without aura, but he never accompanied other clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine

Baek

Weigand

et al. 2014

Eur J Hum Genet

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Hereditary sensorineural hearing loss is an extremely clinical and genetic heterogeneous disorder in humans. Especially, syndromic hearing loss is subdivided by combinations of various phenotypes, and each subtype is related to different genes. We present a new form of progressive hearing loss with migraine found to be associated with a variant in the ATP1A2 gene. The ATP1A2 gene has been reported as the major genetic cause of familial migraine by several previous studies. A Korean family presenting progressive hearing loss with migraine was ascertained. The affected members did not show any aura or other neurologic symptoms during migraine attacks, indicating on a novel phenotype of syndromic hearing loss. To identify the causative gene, linkage analysis and whole-exome sequencing were performed. A novel missense variant, c.571G4A (p.(Val191Met)), was identified in the ATP1A2 gene that showed co-segregation with the phenotype in the family. In silico studies suggest that this variant causes a change in hydrophobic interactions and thereby slightly destabilize the A-domain of Na þ /K þ -ATPase. However, functional studies failed to show any effect of the p.(Val191Met) substitution on the catalytic rate of this enzyme. We describe a new phenotype of progressive hearing loss with migraine associated with a variant in the ATP1A2 gene. This study suggests that a variant in Na þ /K þ -ATPase can be involved in both migraine and hearing loss.

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Migraine genetics: An update

Cited by 46 publications

References 93 publications

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis

Familial Hemiplegic Migraine

A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine

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