Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine
ObjectiveWe admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlatio...
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| Format: | Article |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1159649/full |
| _version_ | 1797843476831797248 |
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| author | Xiaoyue Hu Miao Jing Yanping Wang Yanshan Liu Ying Hua |
| author_facet | Xiaoyue Hu Miao Jing Yanping Wang Yanshan Liu Ying Hua |
| author_sort | Xiaoyue Hu |
| collection | DOAJ |
| description | ObjectiveWe admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response.MethodsWe described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant.ResultsWES identified a novel de novo SCN2A variant (c.468 G > C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that SCN2A-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na+ channel, all of which suggested a loss-of-function (LOF) of Nav1.2 channel.ConclusionWe showed the importance of functional analysis for a SCN2A variant with unknown significance to determine pathogenicity, drug reactions, and genotype–phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some SCN2A-related epilepsies requires vigilance to assess the possibility of epilepsy worsening. |
| first_indexed | 2024-04-09T17:05:52Z |
| format | Article |
| id | doaj.art-e7695c69d9ad481ba1b23da907ed82d6 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-09T17:05:52Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-e7695c69d9ad481ba1b23da907ed82d62023-04-20T16:47:39ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-04-011610.3389/fnmol.2023.11596491159649Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepineXiaoyue Hu0Miao Jing1Yanping Wang2Yanshan Liu3Ying Hua4Department of Neurology, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, ChinaDepartment of Neurology, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, ChinaDepartment of Neurology, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, ChinaDepartment of Pediatric Laboratory, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, ChinaDepartment of Neurology, Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital), Wuxi, ChinaObjectiveWe admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response.MethodsWe described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant.ResultsWES identified a novel de novo SCN2A variant (c.468 G > C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that SCN2A-K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na+ channel, all of which suggested a loss-of-function (LOF) of Nav1.2 channel.ConclusionWe showed the importance of functional analysis for a SCN2A variant with unknown significance to determine pathogenicity, drug reactions, and genotype–phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some SCN2A-related epilepsies requires vigilance to assess the possibility of epilepsy worsening.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1159649/fullearly-onset epileptic encephalopathySCN2Aoxcarbazepinepatch-clampprecise medicine |
| spellingShingle | Xiaoyue Hu Miao Jing Yanping Wang Yanshan Liu Ying Hua Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine Frontiers in Molecular Neuroscience early-onset epileptic encephalopathy SCN2A oxcarbazepine patch-clamp precise medicine |
| title | Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine |
| title_full | Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine |
| title_fullStr | Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine |
| title_full_unstemmed | Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine |
| title_short | Functional analysis of a novel de novo SCN2A variant in a patient with seizures refractory to oxcarbazepine |
| title_sort | functional analysis of a novel de novo scn2a variant in a patient with seizures refractory to oxcarbazepine |
| topic | early-onset epileptic encephalopathy SCN2A oxcarbazepine patch-clamp precise medicine |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1159649/full |
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