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

• Published in: Journal of the neurological sciences Vol. 301; no. 1; pp. 90 - 92
• Main Authors: Dabby, Ron, Sadeh, Menachem, Gilad, Ronit, Lampl, Yair, Cohen, Sarit, Inbar, Shani, Leshinsky-Silver, Esther
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15.02.2011; Elsevier
• Subjects: Aged; Amino Acid Sequence; Amino Acid Substitution; Biological and medical sciences; Chronic Disease; Conserved Sequence; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Exons - genetics; Female; Heterozygote; Humans; Jews - genetics; Medical sciences; Models, Molecular; Molecular Sequence Data; Mutant Proteins - chemistry; Mutant Proteins - genetics; Mutant Proteins - physiology; Mutation, Missense; Nav1.7; NAV1.7 Voltage-Gated Sodium Channel; Neuralgia - genetics; Neuralgia - physiopathology; Neurology; Neuropathic pain; Phenotype; Point Mutation; SCN9A; Sequence Alignment; Sequence Homology, Amino Acid; Sodium Channels - chemistry; Sodium Channels - genetics; Sodium Channels - physiology; Nav1.7; SCN9A; Neuropathic pain; Chronic; Nervous system diseases; Phenotype; Pain; Sodium; Mutation; Neuralgia; Neurological disorder
• ISSN: 0022-510X; 1878-5883; 1878-5883
• DOI: 10.1016/j.jns.2010.10.006

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. To investigate mutations in the SCN9A gene in patients with chronic non-paroxysmal neuropathic pain. 9 patients with chronic severe unexplained neuropathic pain. 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. SCN9A mutations cause pain syndromes other than IEM and PEPD. These mutations should be considered in patients with resistant unexplained chronic neuropathic pain.