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Casein kinase i? mutations in familial migraine and advanced sleep phase.

ABSTRACT: Migraine is a common disabling disorder with a significant genetic component, characterized by severe headache and often accompanied by nausea, vomiting, and light sensitivity. We identified two families, each with a distinct missense mutation in the gene encoding casein kinase I? (CKI?), in which the mutation cosegregated with both the presence of migraine and advanced sleep phase. The resulting alterations (T44A and H46R) occurred in the conserved catalytic domain of CKI?, where they caused reduced enzyme activity. Mice engineered to carry the CKI?-T44A allele were more sensitive to pain after treatment with the migraine trigger nitroglycerin. CKI?-T44A mice also exhibited a reduced threshold for cortical spreading depression (believed to be the physiological analog of migraine aura) and greater arterial dilation during cortical spreading depression. Astrocytes from CKI?-T44A mice showed increased spontaneous and evoked calcium signaling. These genetic, cellular, physiological, and behavioral analyses suggest that decreases in CKI? activity can contribute to the pathogenesis of migraine.

SUBMITTER: Brennan KC

PROVIDER: S-EPMC4220792 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Casein kinase iδ mutations in familial migraine and advanced sleep phase.

Brennan K C KC Bates Emily A EA Shapiro Robert E RE Zyuzin Jekaterina J Hallows William C WC Huang Yong Y Lee Hsien-Yang HY Jones Christopher R CR Fu Ying-Hui YH Charles Andrew C AC Ptáček Louis J LJ

Science translational medicine 20130501 183

Migraine is a common disabling disorder with a significant genetic component, characterized by severe headache and often accompanied by nausea, vomiting, and light sensitivity. We identified two families, each with a distinct missense mutation in the gene encoding casein kinase Iδ (CKIδ), in which the mutation cosegregated with both the presence of migraine and advanced sleep phase. The resulting alterations (T44A and H46R) occurred in the conserved catalytic domain of CKIδ, where they caused re ...[more]

PMID: 23636092

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Project description:BACKGROUND:It is unknown whether clinical parameters differ between migraineurs with and without first-degree family members with migraine. OBJECTIVES:The present cross-sectional study describes differences between familial and sporadic migraine with a focus on migraine characteristics, migraine severity, comorbidities, and treatment. METHOD:From the Danish Headache Center we recruited 358 patients with familial migraine and 1727 patients with sporadic migraine. Each participant was assessed using a validated semi-structured interview. RESULTS:No differences in age (Mean = 44 and 44 [SD = 12.28 and 12.58] for familial and sporadic migraineurs, respectively; P = .900) or sex (295/358 (82.4%) and 1413/1727 (81.8%) women in familial and sporadic migraineurs, respectively; P = .853) were found. Familial migraineurs had more aphasic aura than sporadic migraineurs (41% vs 27%, P = .001). Sporadic migraineurs had more lifetime attacks ie, >100 attacks (45% vs 70%, P < .001) and prolonged attacks ie, lasting >72 hours (5% vs 12%, P < .001) than familial migraineurs. Further, sporadic migraineurs had a higher incidence of concussions (37% vs 41%, P = .001) compared to familial migraineurs. In agreement with a previous study, there was no difference between familial and sporadic migraine regarding triptan response (84% vs 81%, P = .440). CONCLUSION:Headache characteristics, triptan response, and comorbidities where similar in individulas with and without inherited migraine, suggesting that migraine are to be considered a hmogenoues disease. The difference in the clinical presentation of migraine with aura symptoms among patients with familial migraine should be considered in future studies. Further, more severe migraine among patients with sporadic migraine with aura could suggest that sporadic migraineurs have been exposed to stronger or multiple environmental factors and indicate that an early intervention in migraine treatment could lessen the severity of migraine.

Dataset Information

Casein kinase i? mutations in familial migraine and advanced sleep phase.

Publications

Casein kinase iδ mutations in familial migraine and advanced sleep phase.

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