title: The Revolution in Migraine Genetics: From Aching Channels Disorders to a Next-Generation Medicine.
abstract: Channelopathies are a heterogeneous group of neurological disorders resulting from dysfunction of ion channels located in cell membranes and organelles. The clinical scenario is broad and symptoms such as generalized epilepsy (with or without fever), migraine (with or without aura), episodic ataxia and periodic muscle paralysis are some of the best known consequences of gain- or loss-of-function mutations in ion channels. We review the main clinical effects of ion channel mutations associated with a significant impact on migraine headache. Given the increasing and evolving use of genetic analysis in migraine research-greater emphasis is now placed on genetic markers of dysfunctional biological systems-we also show how novel information in rare monogenic forms of migraine might help to clarify the disease mechanisms in the general population of migraineurs. Next-generation sequencing (NGS) and more accurate and precise phenotyping strategies are expected to further increase understanding of migraine pathophysiology and genetics.
authors.affiliation: Clinical Neurophysiology Laboratory, IRCCS Stella Maris Foundation Pisa, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pellacani
authors.affiliation: Clinical Neurophysiology Laboratory, IRCCS Stella Maris FoundationPisa, Italy; Molecular Medicine, IRCCS Stella Maris FoundationPisa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Sicca
authors.affiliation: Don Carlo Gnocchi Onlus Foundation Milan, Italy.
authors.forename: Cherubino
authors.initials: C
authors.lastname: Di Lorenzo
authors.affiliation: Genomic and Post-Genomic Center, C. Mondino National Institute of Neurology Pavia, Italy.
authors.forename: Gaetano S
authors.initials: GS
authors.lastname: Grieco
authors.affiliation: Clinical Neurophysiology Laboratory, IRCCS Stella Maris Foundation Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Valvo
authors.affiliation: Genomic and Post-Genomic Center, C. Mondino National Institute of Neurology Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.affiliation: Molecular Medicine, IRCCS Stella Maris Foundation Pisa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rubegni
authors.affiliation: Molecular Medicine, IRCCS Stella Maris Foundation Pisa, Italy.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
keywords: astrocyte; calcium channel; glutamate; migraine; sodium channel; tripartite synapse