Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine

Vries, Boukje de; Freilinger, Tobias; Vanmolkot, Kaate R J; Koenderink, Jan B.; Stam, AH; Terwindt, Gisela M.; Babini, Elena; Boogerd, Eelke H van den; Heuvel, Jeroen J. M. W. van den; Frants, Rune R.; Haan, Joost; Pusch, Michael; Maagdenberg, Arn M. J. M. van den; Ferrari, Michel D.; Dichgans, Martin

doi:10.1212/01.wnl.0000295670.01629.5a

Cited by 107 publications

(98 citation statements)

References 33 publications

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“…28 Population-based family studies and twin studies support that importance of genetic factors in migraine, and mutations in genes including CACNA1A, ATP1A2, or SCN1A have been identified as the causes of the FHM and SHM. 9,20,[29][30][31] Thus to date, genes have been identified in rare subtypes of migraine, but not in the more common subtypes of migraine. In the present study, our results address that a more common type of migraine, migraine without aura, can be caused by a mutation of the ATP1A2 gene.…”

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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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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“…Although it was not detected in controls, this region is not conserved among different species, which could suggest that it represents a polymorphism. There are few reports of mutations in FHM genes in SHM patients 4,10 . Phenotype-genotype correlations in these patients and family members demonstrated the presence of mutation carriers in migraine with aura (or in individuals without migraine) 4,10 .…”

Section: Discussionmentioning

confidence: 99%

“…We performed sequencing of the coding regions and exon-intron boundaries of the genes previously associated with FHM (CACNA1A, ATP1A2, SCN1A) 4 , including the promoter regions for the first two. Analyses showed only one alteration in exon 8 of ATP1A2, a heterozygous deletion of 3 nucleotides (TTC) predicting F304del in the encoded protein (Fig 2A).…”

Section: Mutation Screeningmentioning

confidence: 99%

Migrainous infarction as a complication of sporadic hemiplegic migraine in childhood

Ribeiro

Pinto

Villa

et al. 2009

Arq. Neuro-Psiquiatr.

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According to the second edition of the International Classification of Headache Disorders (ICHD-II) 1 , migrainous infarction (MI) is a complication of migraine with aura. MI is diagnosed when one or more aura symptoms last longer than 60 minutes, and neuroradiological studies demonstrate ischemic stroke that potentially explains the symptoms. Stroke should not be attributed to another disorder. The ICHD-II also defines sporadic hemiplegic migraine (SHM) as a subtype of migraine with aura associated with fully reversible motor weakness in association to the typical aura symptoms (visual, sensory or dysphasic aura). Unlike familial hemiplegic migraine (FHM), familial history of migraine with motor weakness in first-or second-degree relatives is absent. MI in childhood is very rare and epidemiological studies are scarce 2 . Reports of incidence of migrainous stroke in this group range from 0.5% 2 to 1.7% 3. A fairly and diligent review of the literature found no previous reports of MI during childhood following SHM in Brazil.Herein we report a case of MI following SHM in a child. We obtained written informed consent to publish the case, as well as the results of genetic testing. The principles outlined in the declaration of Helsinki were followed. CASEA 10-year-old boy was initially referred to our service on May of 2004, with a 2-year history of attacks of bifrontal and throbbing headache, preceded by right hemi-hypoesthesia and hemiparesis that typically lasted less than 60 minutes. Headache attacks were of moderate intensity and were associated with photophobia and phonophobia. Frequency was around 3 per month and duration ranged from 10 to 72 hours.Family reported a single episode of headache in which the associated right hemiparesis lasted about three days. Although attack was longer and clearly not suggestive of a benign migraine attack, it had not been investigated.The patient had no relevant prior medical history. Relevant familial history included mother suffering from migraine with visual aura, and brother with a past episode of transient left hemiparesis (without headache) in the context of varicella infection.Two months before the first consultation, patient suffered a partial seizure, characterized by right hemi-body hypertonia, cephalic deviation and gaze shift to the right side, during a typical attack of hemiplegic migraine. Patient recovered totally and neurological exam was normal. Magnetic resonance imaging revealed a left thalamic (pulvinar) lesion, suggestive of ischemia (Fig 1). The patient was then referred to our division for investigation and treatment.A comprehensive complementary investigation with blood tests, imaging tests, genetic tests, EEG and CSF for ischemic stroke was performed and revealed no abnormalities. Treatment with flunarizine yielded adequate control of the migraine attacks, but it was suspended due to significant drowsiness and weight gain. Patient responded well to propranolol and is free of headaches since then (headache free for 2 years). Mutation screeningScreening ...

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“…According to foreign researchers [13,14], the genetic component in migraine with aura is stronger than that in migraine without aura. Some authors define migraine as a polygenic multiple-factor disease [15,16].…”

Section: Inheritance Of Migrainementioning

confidence: 99%

Genetics of Migraine - Is There any Progress?

Klimov¹,

Kondratieva²,

Анучина³

et al. 2017

JNSK

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Nowadays migraine ranks 9th in the list of leading causes of disability among population. In Russia migraine prevalence is two times higher than the world index and inflicts a considerable damage on the state economy. Despite almost one-century history of studying migraine, science until now cannot explain many cases of attack occurrence. It causes difficulties both for diagnosis and treatment -the therapy of patients with migraine is not sufficiently effective. Today one of the investigation directions is searching of migraine biomarkers confirming diagnosis. In this review we attempted to generalize the results of available works targeted at searching genetic markers of migraine.

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Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic migraine

Cited by 107 publications

References 33 publications

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

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

Migrainous infarction as a complication of sporadic hemiplegic migraine in childhood

Genetics of Migraine - Is There any Progress?

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