Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy
Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels. In this study, we assessed the role of fifteen other ion channels in neuropathic pain. Patients with SFN (n = 414) were analyzed...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/22/14095 |
| Summary: | Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels. In this study, we assessed the role of fifteen other ion channels in neuropathic pain. Patients with SFN (n = 414) were analyzed for <i>ANO1</i>, <i>ANO3</i>, <i>HCN1</i>, <i>KCNA2</i>, <i>KCNA4</i>, <i>KCNK18</i>, <i>KCNN1</i>, <i>KCNQ3</i>, <i>KCNQ5</i>, <i>KCNS1</i>, <i>TRPA1</i>, <i>TRPM8</i>, <i>TRPV1</i>, <i>TRPV3</i> and <i>TRPV4</i> variants by single-molecule molecular inversion probes–next-generation sequencing. These patients did not have genetic variants in <i>SCN3A</i>, <i>SCN7A-SCN11A</i> and <i>SCN1B-SCN4B</i>. In twenty patients (20/414, 4.8%), a potentially pathogenic heterozygous variant was identified in an ion-channel gene (ICG). Variants were present in seven genes, for two patients (0.5%) in <i>ANO3</i>, one (0.2%) in <i>KCNK18</i>, two (0.5%) in <i>KCNQ3</i>, seven (1.7%) in <i>TRPA1</i>, three (0.7%) in <i>TRPM8</i>, three (0.7%) in <i>TRPV1</i> and two (0.5%) in <i>TRPV3</i>. Variants in the TRP genes were the most frequent (n = 15, 3.6%), partly in patients with high mean maximal pain scores VAS = 9.65 ± 0.7 (n = 4). Patients with ICG variants reported more severe pain compared to patients without such variants (VAS = 9.36 ± 0.72 vs. VAS = 7.47 ± 2.37). This cohort study identified ICG variants in neuropathic pain in SFN, complementing previous findings of ICG variants in diabetic neuropathy. These data show that ICG variants are central in neuropathic pain of different etiologies and provides promising gene candidates for future research. |
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| ISSN: | 1661-6596 1422-0067 |