title: Sodium channel genes in pain-related disorders: phenotype-genotype associations and recommendations for clinical use.
abstract: Human studies have firmly implicated voltage-gated sodium channels in human pain disorders, and targeted and massively parallel genomic sequencing is beginning to be used in clinical practice to determine which sodium channel variants are involved. Missense substitutions of SCN9A, the gene encoding sodium channel NaV1.7, SCN10A, the gene encoding sodium channel NaV1.8, and SCN11A, the gene encoding sodium channel NaV1.9, produce gain-of-function changes that contribute to pain in many human painful disorders. Genomic sequencing might help to establish a diagnosis, and in the future might support individualisation of therapeutic approaches. However, in many cases, and especially in sodium channelopathies, the results from genomic sequencing can only be appropriately interpreted in the context of an extensive functional assessment, or family segregation analysis of phenotype and genotype.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT, USA. Electronic address: stephen.waxman@yale.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.affiliation: Department of Neurology, Spaarne Hospital, Hoofddorp, Netherlands; Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Ingemar S J
authors.initials: ISJ
authors.lastname: Merkies
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Monique M
authors.initials: MM
authors.lastname: Gerrits
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA; Center for Neuroscience and Regeneration Research, Veterans Affairs Medical Center, West Haven, CT, USA.
authors.forename: Sulayman D
authors.initials: SD
authors.lastname: Dib-Hajj
authors.affiliation: Neuroalgology and Headache Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.affiliation: Molecular Nociception Group, University College London, London, UK.
authors.forename: James J
authors.initials: JJ
authors.lastname: Cox
authors.affiliation: Molecular Nociception Group, University College London, London, UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Wood
authors.affiliation: Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands.
authors.forename: Joost P H
authors.initials: JPH
authors.lastname: Drenth
authors.affiliation: Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands.
authors.forename: Catharina G
authors.initials: CG
authors.lastname: Faber
mesh_terms: D000818:Animals; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D010146:Pain / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D017410:Practice Guidelines as Topic; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels