Chronic non-paroxysmal neuropathic pain - Novel phenotype of mutation in the sodium channel SCN9A gene

J Neurol Sci. 2011 Feb 15;301(1-2):90-2. doi: 10.1016/j.jns.2010.10.006. Epub 2010 Nov 20.

Abstract

Background: Gain-of-function mutations in the SCN9A gene (encoding to NaV1.7 voltage-gated sodium channel) cause two rare paroxysmal pain disorders: inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEDP). These phenotypes are characterized by episodic extreme localized pain with cutaneous autonomic signs. So far, no other phenotypes have been associated with mutation in the SCN9A gene.

Objective: To investigate mutations in the SCN9A gene in patients with chronic non-paroxysmal neuropathic pain.

Patients: 9 patients with chronic severe unexplained neuropathic pain.

Results: Of the nine patients one had predicted pathologic mutations in the SCN9A gene. This patient had a heterozygous change of n.4648 T-C in exon 27 resulting in a substitution of W1550R, a highly conserved amino acid, predicting damage in the transmembrane S2 region, repeat IV. This mutation was not found in 50 controls.

Conclusions: SCN9A mutations cause pain syndromes other than IEM and PEPD. These mutations should be considered in patients with resistant unexplained chronic neuropathic pain.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Chronic Disease
  • Conserved Sequence
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Heterozygote
  • Humans
  • Jews / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / physiology
  • Mutation, Missense*
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neuralgia / genetics*
  • Neuralgia / physiopathology
  • Phenotype
  • Point Mutation*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sodium Channels / chemistry
  • Sodium Channels / genetics*
  • Sodium Channels / physiology

Substances

  • Mutant Proteins
  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Sodium Channels