Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients
Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic <i>CHD2</i> variants. While only a few pathogenic <i>CHD2</i> variants have been reported with deta...
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MDPI AG
2022-05-01
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| author | Xu Wang Di Cui Changhong Ding Chunhong Chen Xiaohui Wang Fang Fang Hong Jin Xiaotun Ren |
| author_facet | Xu Wang Di Cui Changhong Ding Chunhong Chen Xiaohui Wang Fang Fang Hong Jin Xiaotun Ren |
| author_sort | Xu Wang |
| collection | DOAJ |
| description | Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic <i>CHD2</i> variants. While only a few pathogenic <i>CHD2</i> variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic <i>CHD2</i> variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two <i>de novo</i> (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this <i>CHD2</i> variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of <i>CHD2</i>-related epileptic encephalopathy. |
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| spelling | doaj.art-3c6398000963441aa39f84a8c32232f92023-11-23T11:11:25ZengMDPI AGGenes2073-44252022-05-0113590810.3390/genes13050908Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese PatientsXu Wang0Di Cui1Changhong Ding2Chunhong Chen3Xiaohui Wang4Fang Fang5Hong Jin6Xiaotun Ren7Department of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaRunning Gene Inc., Beijing, 100085, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDepartment of Neurology, Beijing Children’s Hospital, Capital Medical University, National Centre for Children’s Health, Beijing 100045, ChinaDevelopmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic <i>CHD2</i> variants. While only a few pathogenic <i>CHD2</i> variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic <i>CHD2</i> variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two <i>de novo</i> (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this <i>CHD2</i> variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of <i>CHD2</i>-related epileptic encephalopathy.https://www.mdpi.com/2073-4425/13/5/908epileptic encephalopathy (EE)chromodomain-helicase-DNA-binding protein 2 (CHD2)childhood-onset epileptic encephalopathy (DEE94)seizuredevelopmental delayintellectual disability (ID) |
| spellingShingle | Xu Wang Di Cui Changhong Ding Chunhong Chen Xiaohui Wang Fang Fang Hong Jin Xiaotun Ren Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients Genes epileptic encephalopathy (EE) chromodomain-helicase-DNA-binding protein 2 (CHD2) childhood-onset epileptic encephalopathy (DEE94) seizure developmental delay intellectual disability (ID) |
| title | Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients |
| title_full | Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients |
| title_fullStr | Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients |
| title_full_unstemmed | Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients |
| title_short | Novel Loss-of-Function Variants in <i>CHD2</i> Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients |
| title_sort | novel loss of function variants in i chd2 i cause childhood onset epileptic encephalopathy in chinese patients |
| topic | epileptic encephalopathy (EE) chromodomain-helicase-DNA-binding protein 2 (CHD2) childhood-onset epileptic encephalopathy (DEE94) seizure developmental delay intellectual disability (ID) |
| url | https://www.mdpi.com/2073-4425/13/5/908 |
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