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Gain-of-function Na(v)1.8 mutations in painful neuropathy
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, 109(47), 19444-19449. National Academy of Sciences, Proceedings of the National Academy of Sciences of the U.S.A., 109(47), 19444-19449. National Academy of Sciences
- Publication Year :
- 2012
-
Abstract
- Painful peripheral neuropathy often occurs without apparent underlying cause. Gain-of-function variants of sodium channel Na v 1.7 have recently been found in ∼30% of cases of idiopathic painful small-fiber neuropathy. Here, we describe mutations in Na v 1.8, another sodium channel that is specifically expressed in dorsal root ganglion (DRG) neurons and peripheral nerve axons, in patients with painful neuropathy. Seven Na v 1.8 mutations were identified in 9 subjects within a series of 104 patients with painful predominantly small-fiber neuropathy. Three mutations met criteria for potential pathogenicity based on predictive algorithms and were assessed by voltage and current clamp. Functional profiling showed that two of these three Na v 1.8 mutations enhance the channel’s response to depolarization and produce hyperexcitability in DRG neurons. These observations suggest that mutations of Na v 1.8 contribute to painful peripheral neuropathy.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
DNA Mutational Analysis
medicine.disease_cause
patch clamp
Nav1.9
NAV1.8 Voltage-Gated Sodium Channel
Mice
Nerve Fibers
Dorsal root ganglion
Ganglia, Spinal
medicine
Animals
Humans
Patch clamp
Aged
Mutation
Multidisciplinary
business.industry
Sodium channel
dorsal root ganglia
Biological Sciences
medicine.disease
Electrophysiological Phenomena
medicine.anatomical_structure
Peripheral neuropathy
Amino Acid Substitution
NAV1
Neuralgia
business
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America, 109(47), 19444-19449. National Academy of Sciences, Proceedings of the National Academy of Sciences of the U.S.A., 109(47), 19444-19449. National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....52bd76b44abf61c0a83b747ebff5432b