title: From migraine genes to mechanisms.
abstract: Migraine is a common multifactorial episodic brain disorder with strong genetic basis. Monogenic subtypes include rare familial hemiplegic migraine, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, familial advanced sleep-phase syndrome (FASPS), and retinal vasculopathy with cerebral leukodystrophy. Functional studies of disease-causing mutations in cellular and/or transgenic models revealed enhanced (glutamatergic) neurotransmission and abnormal vascular function as key migraine mechanisms. Common forms of migraine (both with and without an aura), instead, are thought to have a polygenic makeup. Genome-wide association studies have already identified over a dozen genes involved in neuronal and vascular mechanisms. Here, we review the current state of molecular genetic research in migraine, also with respect to functional and pathway analyses. We will also discuss how novel experimental approaches for the identification and functional characterization of migraine genes, such as next-generation sequencing, induced pluripotent stem cell, and optogenetic technologies will further our understanding of the molecular pathways involved in migraine pathogenesis.
authors: Departments of Neurology and Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Else A
authors: EA
authors: Tolner
authors: Thijs
authors: T
authors: Houben
authors: Gisela M
authors: GM
authors: Terwindt
authors: Boukje
authors: B
authors: de Vries
authors: Michel D
authors: MD
authors: Ferrari
authors: Arn M J M
authors: AMJM
authors: van den Maagdenberg
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D004195:Disease Models, Animal; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008881:Migraine Disorders / Q000235:genetics* / Q000503:physiopathology; D020412:Multifactorial Inheritance / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D005819:Genetic Markers; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type