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: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/22/14095 |
| _version_ | 1797465088407371776 |
|---|---|
| author | Milena Ślęczkowska Rowida Almomani Margherita Marchi Erika Salvi Bianca T A de Greef Maurice Sopacua Janneke G J Hoeijmakers Patrick Lindsey Stephen G Waxman Giuseppe Lauria Catharina G Faber Hubert J M Smeets Monique M Gerrits |
| author_facet | Milena Ślęczkowska Rowida Almomani Margherita Marchi Erika Salvi Bianca T A de Greef Maurice Sopacua Janneke G J Hoeijmakers Patrick Lindsey Stephen G Waxman Giuseppe Lauria Catharina G Faber Hubert J M Smeets Monique M Gerrits |
| author_sort | Milena Ślęczkowska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T18:16:27Z |
| format | Article |
| id | doaj.art-2de82955c0494f2b8af1fe0d6215c9f8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:16:27Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2de82955c0494f2b8af1fe0d6215c9f82023-11-24T08:38:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221409510.3390/ijms232214095Peripheral Ion Channel Genes Screening in Painful Small Fiber NeuropathyMilena Ślęczkowska0Rowida Almomani1Margherita Marchi2Erika Salvi3Bianca T A de Greef4Maurice Sopacua5Janneke G J Hoeijmakers6Patrick Lindsey7Stephen G Waxman8Giuseppe Lauria9Catharina G Faber10Hubert J M Smeets11Monique M Gerrits12Department of Toxicogenomics, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 ER Maastricht, The NetherlandsNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyNeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 ER Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 ER Maastricht, The NetherlandsDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Neurology, Yale University School of Medicine, New Haven, CT 06510, USANeuroalgology Unit, IRCCS Foundation “Carlo Besta” Neurological Institute, 20133 Milan, ItalyDepartment of Neurology, School of Mental Health and Neuroscience, Maastricht University Medical Centre+, 6229 ER Maastricht, The NetherlandsDepartment of Toxicogenomics, Maastricht University, 6229 ER Maastricht, The NetherlandsDepartment of Clinical Genetics, Maastricht University Medical Centre+, 6229 HX Maastricht, The NetherlandsNeuropathic 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.https://www.mdpi.com/1422-0067/23/22/14095idiopathic small fiber neuropathyion channelMIPs-NGSneuropathic painperipheral neuropathy |
| spellingShingle | Milena Ślęczkowska Rowida Almomani Margherita Marchi Erika Salvi Bianca T A de Greef Maurice Sopacua Janneke G J Hoeijmakers Patrick Lindsey Stephen G Waxman Giuseppe Lauria Catharina G Faber Hubert J M Smeets Monique M Gerrits Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy International Journal of Molecular Sciences idiopathic small fiber neuropathy ion channel MIPs-NGS neuropathic pain peripheral neuropathy |
| title | Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy |
| title_full | Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy |
| title_fullStr | Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy |
| title_full_unstemmed | Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy |
| title_short | Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy |
| title_sort | peripheral ion channel genes screening in painful small fiber neuropathy |
| topic | idiopathic small fiber neuropathy ion channel MIPs-NGS neuropathic pain peripheral neuropathy |
| url | https://www.mdpi.com/1422-0067/23/22/14095 |
| work_keys_str_mv | AT milenasleczkowska peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT rowidaalmomani peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT margheritamarchi peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT erikasalvi peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT biancatadegreef peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT mauricesopacua peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT jannekegjhoeijmakers peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT patricklindsey peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT stephengwaxman peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT giuseppelauria peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT catharinagfaber peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT hubertjmsmeets peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy AT moniquemgerrits peripheralionchannelgenesscreeninginpainfulsmallfiberneuropathy |