KCNC2 variants of uncertain significance are also associated to various forms of epilepsy
Recently, de novo variants in KCNC2, coding for the potassium channel subunit KV3.2, have been described as causative for various forms of epilepsy including genetic generalized epilepsy (GGE) and developmental and epileptic encephalopathy (DEE). Here, we report the functional characteristics of thr...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1212079/full |
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| author | Simone Seiffert Simone Seiffert Manuela Pendziwiat Manuela Pendziwiat Ulrike B. S. Hedrich Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Yvonne Weber Yvonne Weber Niklas Schwarz |
| author_facet | Simone Seiffert Simone Seiffert Manuela Pendziwiat Manuela Pendziwiat Ulrike B. S. Hedrich Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Yvonne Weber Yvonne Weber Niklas Schwarz |
| author_sort | Simone Seiffert |
| collection | DOAJ |
| description | Recently, de novo variants in KCNC2, coding for the potassium channel subunit KV3.2, have been described as causative for various forms of epilepsy including genetic generalized epilepsy (GGE) and developmental and epileptic encephalopathy (DEE). Here, we report the functional characteristics of three additional KCNC2 variants of uncertain significance and one variant classified as pathogenic. Electrophysiological studies were performed in Xenopus laevis oocytes. The data presented here support that KCNC2 variants with uncertain significance may also be causative for various forms of epilepsy, as they show changes in the current amplitude and activation and deactivation kinetics of the channel, depending on the variant. In addition, we investigated the effect of valproic acid on KV3.2, as several patients carrying pathogenic variants in the KCNC2 gene achieved significant seizure reduction or seizure freedom with this drug. However, in our electrophysiological investigations, no change on the behavior of KV3.2 channels could be observed, suggesting that the therapeutic effect of VPA may be explained by other mechanisms. |
| first_indexed | 2024-03-13T06:36:35Z |
| format | Article |
| id | doaj.art-f35535cc4a4a40148a114289331ac4de |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-13T06:36:35Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-f35535cc4a4a40148a114289331ac4de2023-06-09T05:13:56ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-06-011410.3389/fneur.2023.12120791212079KCNC2 variants of uncertain significance are also associated to various forms of epilepsySimone Seiffert0Simone Seiffert1Manuela Pendziwiat2Manuela Pendziwiat3Ulrike B. S. Hedrich4Ingo Helbig5Ingo Helbig6Ingo Helbig7Ingo Helbig8Ingo Helbig9Yvonne Weber10Yvonne Weber11Niklas Schwarz12Department of Human Genetics, University Hospital Ulm, Ulm, GermanyDepartment of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, GermanyDepartment of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, GermanyDepartment of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyDepartment of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel, GermanyDivision of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesThe Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Biomedical and Health Informatics (DBHi), Children’s Hospital of Philadelphia, Philadelphia, PA, United StatesDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyDepartment of Epileptology and Neurology, University of Aachen, Aachen, GermanyDepartment of Neurology and Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, GermanyRecently, de novo variants in KCNC2, coding for the potassium channel subunit KV3.2, have been described as causative for various forms of epilepsy including genetic generalized epilepsy (GGE) and developmental and epileptic encephalopathy (DEE). Here, we report the functional characteristics of three additional KCNC2 variants of uncertain significance and one variant classified as pathogenic. Electrophysiological studies were performed in Xenopus laevis oocytes. The data presented here support that KCNC2 variants with uncertain significance may also be causative for various forms of epilepsy, as they show changes in the current amplitude and activation and deactivation kinetics of the channel, depending on the variant. In addition, we investigated the effect of valproic acid on KV3.2, as several patients carrying pathogenic variants in the KCNC2 gene achieved significant seizure reduction or seizure freedom with this drug. However, in our electrophysiological investigations, no change on the behavior of KV3.2 channels could be observed, suggesting that the therapeutic effect of VPA may be explained by other mechanisms.https://www.frontiersin.org/articles/10.3389/fneur.2023.1212079/fullpotassium channeldevelopmental and epileptic encephalopathyKCNC2 electrophysiologyfunctional analysisprecision medicine |
| spellingShingle | Simone Seiffert Simone Seiffert Manuela Pendziwiat Manuela Pendziwiat Ulrike B. S. Hedrich Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Ingo Helbig Yvonne Weber Yvonne Weber Niklas Schwarz KCNC2 variants of uncertain significance are also associated to various forms of epilepsy Frontiers in Neurology potassium channel developmental and epileptic encephalopathy KCNC2 electrophysiology functional analysis precision medicine |
| title | KCNC2 variants of uncertain significance are also associated to various forms of epilepsy |
| title_full | KCNC2 variants of uncertain significance are also associated to various forms of epilepsy |
| title_fullStr | KCNC2 variants of uncertain significance are also associated to various forms of epilepsy |
| title_full_unstemmed | KCNC2 variants of uncertain significance are also associated to various forms of epilepsy |
| title_short | KCNC2 variants of uncertain significance are also associated to various forms of epilepsy |
| title_sort | kcnc2 variants of uncertain significance are also associated to various forms of epilepsy |
| topic | potassium channel developmental and epileptic encephalopathy KCNC2 electrophysiology functional analysis precision medicine |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1212079/full |
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