Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1

Carlsson, Anna; Forsgren, Lars; Nylander, Per-Olof; Hellman, Urban; Forsman‐Semb, Kristina; Holmgren, Gösta; Holmberg, Dan; Holmberg, Monica

doi:10.1212/01.wnl.0000036617.04943.96

Cited by 82 publications

(46 citation statements)

References 10 publications

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“…Both forms have a strong genetic basis with complex inheritance [Estevez and Gardner, 2004;Palotie et al, 2002], but according to recent epidemiological data the genetic background of MA is stronger than that of MO [Russell and Olesen, 1995]. Recently, several loci for MA and MO have been identified by genome-wide linkage analyses in single extended pedigrees [Carlsson et al, 2002;Soragna et al, 2003] or a collection of multiplex families (MIM]s 157300, 607498, and 607501) [Bjornsson et al, 2003;Cader et al, 2003;Wessman et al, 2002]. Yet the genes involved in common forms of migraine are unknown.…”

Section: Introductionmentioning

confidence: 99%

Rare missense variants inATP1A2 in families with clustering of common forms of migraine

Todt

Dichgans²,

Jurkat‐Rott

et al. 2005

Hum. Mutat.

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Migraine is a recurrent neurovascular disease. Its two most common forms-migraine without aura (MO) and migraine with aura (MA)-both show familial clustering and a complex pattern of inheritance. Familial hemiplegic migraine (FHM) is a rare monogenic subform caused by mutations in the calcium channel gene CACNA1A or the Na(+)/K(+)-ATPase gene ATP1A2. An involvement of FHM genes in the pathogenesis of common forms of migraine is not proven. We therefore systematically screened ATP1A2 in families with several members affected by MA and/or MO. We identified two novel missense alterations [c.520G>A (p.E174 K) and c.1544G>A (p.C515Y)] in two out of 45 families, which were not found in 520 control chromosomes. Functional studies of these variants in Xenopus oocytes by two-electrode voltage clamp measurements and radiochemical determination of ATPase activity showed that C515Y leads to a complete loss of function comparable with the effect of FHM-mutations whereas for E174 K no functional alteration could be found in the in vitro assays. In conclusion we propose that rare variants in ATP1A2 are involved in the susceptibility to common forms of migraine, because of 1) the absence of alterations in controls, 2) the particular pattern of segregation in both families, 3) the high conservation of mutated residues in Na(+)/K(+)-ATPases, 4) the functional effect of C515Y, and 5) the involvement of ATP1A2 in a monogenic form of migraine.

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Section: Introductionmentioning

confidence: 99%

Rare missense variants inATP1A2 in families with clustering of common forms of migraine

Todt

Dichgans²,

Jurkat‐Rott

et al. 2005

Hum. Mutat.

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“…However, the sequence screen cannot exclude possible intronic mutation that could cause MA in our MA families. Mapping studies of MA show many loci that implies polygenetic nature [Nyholt et al, 2000;Jones et al, 2001;Carlsson et al, 2002;Lea et al, 2002;Wessman et al, 2002;Cader et al, 2003;Soragna et al, 2003;Lea et al, 2005;Russo et al, 2005], and twin studies show clear environmental influence [Ulrich et al, 1999a]. Such multifactorial nature of the disease and the limited power of our data (only promoter and exons sequenced) do not rule out that the CACNA1A or ATP1A2 genes may be involved in MA as a complex trait in some families.…”

Section: Discussionmentioning

confidence: 58%

The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine with aura

Kirchmann

Thomsen

Olesen

2006

American J of Med Genetics Pt B

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Epidemiological studies indicate that migraine with typical aura (MA) has a major genetic component but the genes for MA have not been identified. However, the autosomal dominantly inherited familial hemiplegic migraine (FHM) is often caused by mutations in the CACNA1A or ATP1A2 genes. The aim of the study was to investigate if the CACNA1A or ATP1A2 genes are involved in MA with an apparently autosomal dominant mode of inheritance. From a clinic population diagnosed by a trained physician we recruited 34 extended families (comprising 174 MA patients) with an apparently autosomal dominant mode of inheritance of MA. We performed a linkage analysis of 161 of 174 MA patients and 79 unaffected relatives using a framework marker set of 44 markers for chromosome 1 and 22 markers for chromosome 19. Linkage analysis was made with a non-parametric or autosomal dominant parametric model, either allowing for heterogeneity or not, using an affected only analysis. We identified no linkage to CACNA1A and ATP1A2 loci on chromosome 19 or 1, respectively. Additionally, at least two patients from each family and 92 healthy, unrelated controls were selected for a sequence analysis. We sequenced the 48 exons of CACNA1A and the 23 exons of ATP1A2, including promoter and flanking intron sequences. No polymorphism was identified in the CACNA1A or ATP1A2 genes with a strong correlation to MA. Our study shows that the CACNA1A or ATP1A2 genes are probably not involved in MA. To identify the genes involved in the common forms of migraine, future genetic studies should focus on MA and migraine without aura (MO) and not FHM.

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“…Furthermore, the prevalence of frequent episodic tension-type headache is very similar to that of migraine without aura (men 9% and women 20%) in Denmark [27]. Migraine without aura has multifactorial inheritance, although two families with autosomal dominant inheritance are described in the literature [23,24,[28][29][30]. The concordance rates of frequent episodic tension-type headache suggest that the inheritance is multifactorial, i.e., caused by a combination of genetic and environmental factors.…”

Section: Frequent Episodic Tension-type Headache Is Inheritedmentioning

confidence: 87%

Are infrequent episodic, frequent episodic and chronic tension-type headache inherited? A population-based study of 11 199 twin pairs

2006

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IntroductionThe International Classification of Headache Disorders classifies tension-type headache as infrequent episodic, frequent episodic and chronic tension-type headache [1]. The last year prevalence of infrequent episodic tensiontype headache is 64%; 61% among women and 67% among men [2]. The high prevalence causes a positive family history of infrequent tension-type headache simply J Headache Pain (2006) 7:119-126 DOI 10.1007 Are infrequent episodic, frequent episodic and chronic tension-type headache inherited? A population-based study of 11 199 twin pairs Abstract The objective was to investigate the importance of genetic and environmental factors for infrequent episodic, frequent episodic and chronic tension-type headache. Twin pairs recruited from the population-based Danish Twin Registry received a posted questionnaire. Only twin pairs where both twins replied were included. A total of 3523 monozygotic (MZ), 4150 dizygotic (DZ) same-gender and 3526 DZ opposite-gender twin pairs were included. The prevalence of frequent episodic and chronic tension-type headache was significantly more frequent in women than men, and significantly higher in those with co-occurrence of migraine. The concordance rates were significantly higher in MZ than same-gender DZ twin pairs with no or frequent episodic tension-type headache, while the difference was not significant in chronic tension-type headache. The concordance rates of infrequent episodic tension-type headache in MZ and same-gender DZ twin pairs was significantly different in women but not in men, although the difference was small in both genders. We conclude that genetic factors play a role in no and frequent episodic tension-type headache, while infrequent episodic tensiontype headache is caused primarily by environmental factors. The data regarding chronic tension-type headache were limited, so no firm conclusion could be drawn.

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Identification of a susceptibility locus for migraine with and without aura on 6p12.2-p21.1

Cited by 82 publications

References 10 publications

Rare missense variants inATP1A2 in families with clustering of common forms of migraine

Rare missense variants inATP1A2 in families with clustering of common forms of migraine

The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine with aura

Are infrequent episodic, frequent episodic and chronic tension-type headache inherited? A population-based study of 11 199 twin pairs

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