Sodium channel genes in pain-related disorders

Phenotype-genotype associations and recommendations for clinical use

Stephen G. Waxman, Ingemar S J Merkies, Monique M. Gerrits, Sulayman D. Dib-Hajj, Giuseppe Lauria, James J. Cox, John N. Wood, C. Geoffrey Woods, Joost P H Drenth, Catharina G. Faber

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1152-1160
Number of pages9
JournalThe Lancet Neurology
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Somatoform Disorders
Sodium Channels
Genetic Association Studies
Genes
Channelopathies
Voltage-Gated Sodium Channels
High-Throughput Nucleotide Sequencing
Sodium
Genotype
Phenotype
Pain
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sodium channel genes in pain-related disorders : Phenotype-genotype associations and recommendations for clinical use. / Waxman, Stephen G.; Merkies, Ingemar S J; Gerrits, Monique M.; Dib-Hajj, Sulayman D.; Lauria, Giuseppe; Cox, James J.; Wood, John N.; Woods, C. Geoffrey; Drenth, Joost P H; Faber, Catharina G.

In: The Lancet Neurology, Vol. 13, No. 11, 01.11.2014, p. 1152-1160.

Research output: Contribution to journalArticle

Waxman, SG, Merkies, ISJ, Gerrits, MM, Dib-Hajj, SD, Lauria, G, Cox, JJ, Wood, JN, Woods, CG, Drenth, JPH & Faber, CG 2014, 'Sodium channel genes in pain-related disorders: Phenotype-genotype associations and recommendations for clinical use', The Lancet Neurology, vol. 13, no. 11, pp. 1152-1160. https://doi.org/10.1016/S1474-4422(14)70150-4
Waxman, Stephen G. ; Merkies, Ingemar S J ; Gerrits, Monique M. ; Dib-Hajj, Sulayman D. ; Lauria, Giuseppe ; Cox, James J. ; Wood, John N. ; Woods, C. Geoffrey ; Drenth, Joost P H ; Faber, Catharina G. / Sodium channel genes in pain-related disorders : Phenotype-genotype associations and recommendations for clinical use. In: The Lancet Neurology. 2014 ; Vol. 13, No. 11. pp. 1152-1160.
@article{6f119a08ad6a4798a60770ead711350c,
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.",
author = "Waxman, {Stephen G.} and Merkies, {Ingemar S J} and Gerrits, {Monique M.} and Dib-Hajj, {Sulayman D.} and Giuseppe Lauria and Cox, {James J.} and Wood, {John N.} and Woods, {C. Geoffrey} and Drenth, {Joost P H} and Faber, {Catharina G.}",
year = "2014",
month = "11",
day = "1",
doi = "10.1016/S1474-4422(14)70150-4",
language = "English",
volume = "13",
pages = "1152--1160",
journal = "The Lancet Neurology",
issn = "1474-4422",
publisher = "Lancet Publishing Group",
number = "11",

}

TY - JOUR

T1 - Sodium channel genes in pain-related disorders

T2 - Phenotype-genotype associations and recommendations for clinical use

AU - Waxman, Stephen G.

AU - Merkies, Ingemar S J

AU - Gerrits, Monique M.

AU - Dib-Hajj, Sulayman D.

AU - Lauria, Giuseppe

AU - Cox, James J.

AU - Wood, John N.

AU - Woods, C. Geoffrey

AU - Drenth, Joost P H

AU - Faber, Catharina G.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907992197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907992197&partnerID=8YFLogxK

U2 - 10.1016/S1474-4422(14)70150-4

DO - 10.1016/S1474-4422(14)70150-4

M3 - Article

VL - 13

SP - 1152

EP - 1160

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 11

ER -