Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G
Developmental and epileptic encephalopathies (DEEs) have high genetic heterogeneity, and DEE due to the potassium voltage-gated channel subfamily C member 2 (KCNC2) variant remains poorly understood, given the scarcity of related case studies. We report on two unrelated Chinese patients, an 11-year-...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.950255/full |
| _version_ | 1828355922772099072 |
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| author | Sumei Wang Yejing Yu Xu Wang Xiaolong Deng Jiehui Ma Zhisheng Liu Weiyue Gu Dan Sun |
| author_facet | Sumei Wang Yejing Yu Xu Wang Xiaolong Deng Jiehui Ma Zhisheng Liu Weiyue Gu Dan Sun |
| author_sort | Sumei Wang |
| collection | DOAJ |
| description | Developmental and epileptic encephalopathies (DEEs) have high genetic heterogeneity, and DEE due to the potassium voltage-gated channel subfamily C member 2 (KCNC2) variant remains poorly understood, given the scarcity of related case studies. We report on two unrelated Chinese patients, an 11-year-old boy and a 5-year-old girl, diagnosed with global developmental delay (GDD), intellectual disability (ID), and focal impaired awareness seizure characterized by generalized spike and wave complexes on electroencephalogram (EEG) in the absence of significant brain lesions. Whole-exome sequencing (WES) and electrophysiological analysis were performed to detect genetic variants and evaluate functional changes of the mutant KCNC2, respectively. Importantly, we identified a novel gain-of-function KCNC2 variant, R405G, in both patients. Previously reported variants, V471L, R351K, T437A, and T437N, and novel R405G were found in multiple unrelated patients with DEE, showing consistent genotype–phenotype associations. These findings emphasize that the KCNC2 gene is causative for DEE and facilitates treatment and prognosis in patients with DEE due to KCNC2 mutations. |
| first_indexed | 2024-04-14T02:50:31Z |
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| id | doaj.art-a921e281e82d49039f8fd81d01a84e1a |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-14T02:50:31Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-a921e281e82d49039f8fd81d01a84e1a2022-12-22T02:16:18ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-08-011510.3389/fnmol.2022.950255950255Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405GSumei Wang0Yejing Yu1Xu Wang2Xiaolong Deng3Jiehui Ma4Zhisheng Liu5Weiyue Gu6Dan Sun7Department of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurology, Changchun Children’s Hospital, Changchun, ChinaDepartment of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaChigene (Beijing) Translational Medical Research Center Co. Ltd., Beijing, ChinaDepartment of Pediatric Neurology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDevelopmental and epileptic encephalopathies (DEEs) have high genetic heterogeneity, and DEE due to the potassium voltage-gated channel subfamily C member 2 (KCNC2) variant remains poorly understood, given the scarcity of related case studies. We report on two unrelated Chinese patients, an 11-year-old boy and a 5-year-old girl, diagnosed with global developmental delay (GDD), intellectual disability (ID), and focal impaired awareness seizure characterized by generalized spike and wave complexes on electroencephalogram (EEG) in the absence of significant brain lesions. Whole-exome sequencing (WES) and electrophysiological analysis were performed to detect genetic variants and evaluate functional changes of the mutant KCNC2, respectively. Importantly, we identified a novel gain-of-function KCNC2 variant, R405G, in both patients. Previously reported variants, V471L, R351K, T437A, and T437N, and novel R405G were found in multiple unrelated patients with DEE, showing consistent genotype–phenotype associations. These findings emphasize that the KCNC2 gene is causative for DEE and facilitates treatment and prognosis in patients with DEE due to KCNC2 mutations.https://www.frontiersin.org/articles/10.3389/fnmol.2022.950255/fulldevelopmental and epileptic encephalopathywhole-exome sequencingpotassium channelsKCNC2Kv3.2R405G |
| spellingShingle | Sumei Wang Yejing Yu Xu Wang Xiaolong Deng Jiehui Ma Zhisheng Liu Weiyue Gu Dan Sun Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G Frontiers in Molecular Neuroscience developmental and epileptic encephalopathy whole-exome sequencing potassium channels KCNC2 Kv3.2 R405G |
| title | Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G |
| title_full | Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G |
| title_fullStr | Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G |
| title_full_unstemmed | Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G |
| title_short | Emerging evidence of genotype–phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G |
| title_sort | emerging evidence of genotype phenotype associations of developmental and epileptic encephalopathy due to kcnc2 mutation identification of novel r405g |
| topic | developmental and epileptic encephalopathy whole-exome sequencing potassium channels KCNC2 Kv3.2 R405G |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.950255/full |
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