Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel
Objective: Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort (n = 593) of...
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| Format: | Article |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2018.00515/full |
| _version_ | 1811239826142265344 |
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| author | Meng-Han Tsai Chung-Kin Chan Ying-Chao Chang Chih-Hsiang Lin Chia-Wei Liou Wen-Neng Chang Ching-Ching Ng Kheng-Seang Lim Daw-Yang Hwang |
| author_facet | Meng-Han Tsai Chung-Kin Chan Ying-Chao Chang Chih-Hsiang Lin Chia-Wei Liou Wen-Neng Chang Ching-Ching Ng Kheng-Seang Lim Daw-Yang Hwang |
| author_sort | Meng-Han Tsai |
| collection | DOAJ |
| description | Objective: Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort (n = 593) of common focal non-lesional epilepsy patients.Methods: The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform.Results: Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three SCN1A (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three PRRT2 (two p.Arg217Profs*8 and p.Leu298Pro), two CHRNA4 (p.Ser284Leu, p.Ile321Asn), one DEPDC5 (p.Val516Ter), one PCDH19 (p.Asp233Asn), and one SLC2A1 (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data.Conclusion: Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy. |
| first_indexed | 2024-04-12T13:07:56Z |
| format | Article |
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| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T13:07:56Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-527fa4e63a554ced977fdc8429477b932022-12-22T03:31:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-07-01910.3389/fneur.2018.00515372090Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene PanelMeng-Han Tsai0Chung-Kin Chan1Ying-Chao Chang2Chih-Hsiang Lin3Chia-Wei Liou4Wen-Neng Chang5Ching-Ching Ng6Kheng-Seang Lim7Daw-Yang Hwang8Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, TaiwanGenetics and Molecular Biology, Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, MalaysiaDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung, TaiwanGenetics and Molecular Biology, Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, MalaysiaDivision of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaDivision of Nephrology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, TaiwanObjective: Focal epilepsy is the most common subtype of epilepsies in which the influence of underlying genetic factors is emerging but remains largely uncharacterized. The purpose of this study is to determine the contribution of currently known disease-causing genes in a large cohort (n = 593) of common focal non-lesional epilepsy patients.Methods: The customized focal epilepsy gene panel (21 genes) was based on multiplex polymerase chain reaction (PCR) and sequenced by Illumina MiSeq platform.Results: Eleven variants (1.85%) were considered as pathogenic or likely pathogenic, including seven novel mutations. There were three SCN1A (p.Leu890Pro, p.Arg1636Ter, and p.Met1714Val), three PRRT2 (two p.Arg217Profs*8 and p.Leu298Pro), two CHRNA4 (p.Ser284Leu, p.Ile321Asn), one DEPDC5 (p.Val516Ter), one PCDH19 (p.Asp233Asn), and one SLC2A1 (p.Ser414Ter) variants. Additionally, 16 other rare variants were classified as unknown significance due to inconsistent phenotype or lack of segregation data.Conclusion: Currently known focal epilepsy genes only explained a very small subset of focal epilepsy patients. This indicates that the underlying genetic architecture of focal epilepsies is very heterogeneous and more novel genes are likely to be discovered. Our study highlights the usefulness, challenges and limitations of using the multi-gene panel as a diagnostic test in routine clinical practice in patients with focal epilepsy.https://www.frontiersin.org/article/10.3389/fneur.2018.00515/fullfocal epilepsymultigene paneltargeted resequencingNGSmultiplex PCR |
| spellingShingle | Meng-Han Tsai Chung-Kin Chan Ying-Chao Chang Chih-Hsiang Lin Chia-Wei Liou Wen-Neng Chang Ching-Ching Ng Kheng-Seang Lim Daw-Yang Hwang Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel Frontiers in Neurology focal epilepsy multigene panel targeted resequencing NGS multiplex PCR |
| title | Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel |
| title_full | Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel |
| title_fullStr | Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel |
| title_full_unstemmed | Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel |
| title_short | Molecular Genetic Characterization of Patients With Focal Epilepsy Using a Customized Targeted Resequencing Gene Panel |
| title_sort | molecular genetic characterization of patients with focal epilepsy using a customized targeted resequencing gene panel |
| topic | focal epilepsy multigene panel targeted resequencing NGS multiplex PCR |
| url | https://www.frontiersin.org/article/10.3389/fneur.2018.00515/full |
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