دورية أكاديمية
Broadening the scope of multigene panel analysis for adult epilepsy patients.
| العنوان: | Broadening the scope of multigene panel analysis for adult epilepsy patients. |
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| المؤلفون: | Lee S; Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Kang MK; Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., So KH; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Jang R; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Shin YW; Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Jang SS; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Yoon JG; Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea., Kim S; Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea., Kim M; Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Chu K; Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Lee SK; Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea., Kim KJ; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Baek ST; Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Korea., Lim BC; Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea., Moon J; Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.; Department of Neurology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea. |
| المصدر: | Epilepsia open [Epilepsia Open] 2024 Aug; Vol. 9 (4), pp. 1538-1549. Date of Electronic Publication: 2024 Jul 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101692036 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9239 (Electronic) Linking ISSN: 24709239 NLM ISO Abbreviation: Epilepsia Open Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Hoboken, New Jersey : John Wiley & Sons, Inc., [2016]- |
| مواضيع طبية MeSH: | Epilepsy*/genetics, Humans ; Adult ; Male ; Female ; Mice ; Animals ; TOR Serine-Threonine Kinases/genetics ; Young Adult ; Adolescent ; Middle Aged ; Mutation ; Intellectual Disability/genetics ; Genetic Testing |
| مستخلص: | Objective: Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients. Methods: We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age ≤ 19 years, neuronal migration disorder, and seizure freedom not achieved by dual anti-seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel MTOR truncating variant, we electroporated vectors with different MTOR variants into developing mouse brains. Results: A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: DEPDC5, 15q12-q13 duplication (n = 2), SLC6A1, SYNGAP1, EEF1A2, LGI1, MTOR, KCNQ2, MEF2C, and TSC1 (n = 1). We confirmed the functional impact of a novel truncating mutation in the MTOR gene (c.7570C > T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID/DD or childhood-onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies. Significance: Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID/DD or early-onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background. Plain Language Summary: This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood-onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected. (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.) |
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| معلومات مُعتمدة: | 0320200350 Seoul National University Hospital; 0320210170 Seoul National University Hospital; 0620201110 Samjin Pharmaceutical; 2020-ER6904-01 Korea Disease Control and Prevention Agency |
| فهرسة مساهمة: | Keywords: adult epilepsy; gene panel sequencing; next‐generation sequencing; precision medicine |
| المشرفين على المادة: | EC 2.7.11.1 (TOR Serine-Threonine Kinases) EC 2.7.1.1 (MTOR protein, human) |
| تواريخ الأحداث: | Date Created: 20240701 Date Completed: 20240802 Latest Revision: 20240804 |
| رمز التحديث: | 20240804 |
| مُعرف محوري في PubMed: | PMC11296137 |
| DOI: | 10.1002/epi4.12993 |
| PMID: | 38946282 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2470-9239 |
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| DOI: | 10.1002/epi4.12993 |