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NaV channel variants in patients with painful and nonpainful peripheral neuropathy
- Source :
- Neurology: Genetics
- Publication Year :
- 2017
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2017.
-
Abstract
- Objective:To examine the incidence of nonsynonymous missense variants in SCN9A (NaV1.7), SCN10A (NaV1.8), and SCN11A (NaV1.9) in patients with painful and nonpainful peripheral neuropathy.Methods:Next-generation sequencing was performed on 457 patient DNA samples provided by the Peripheral Neuropathy Research Registry (PNRR). The patient diagnosis was as follows: 278 idiopathic peripheral neuropathy (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy (77% painful and 23% nonpainful).Results:We identified 36 (SCN9A), 31 (SCN10A), and 15 (SCN11A) nonsynonymous missense variants, with 47.7% of patients carrying a low-frequency (minor allele frequency SCN9A haplotype frequencies, between PNRR patients with painful or nonpainful peripheral neuropathy. PNRR patient SCN9A and SCN11A missense variant allele frequencies were not significantly different from the Exome Variant Server, European American (EVS-EA) reference population. For SCN10A, there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations.Conclusions:These results suggest that identification of a genetically defined subpopulation for testing of NaV1.7 inhibitors in patients with peripheral neuropathy is unlikely and that additional factors, beyond expression of previously reported disease “mutations,” are more important for the development of painful neuropathy than previously discussed.
- Subjects :
- 0301 basic medicine
Nonsynonymous substitution
medicine.medical_specialty
Gastroenterology
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Missense mutation
Exome
Allele frequency
Genetics (clinical)
business.industry
Haplotype
medicine.disease
3. Good health
Minor allele frequency
030104 developmental biology
Peripheral neuropathy
Neurology (clinical)
business
Polyneuropathy
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 23767839
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Neurology Genetics
- Accession number :
- edsair.doi.dedup.....2e9937edd2e7d0052bab79da53ed18be