دورية أكاديمية
IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures.
| العنوان: | IFIH1 variants are associated with generalised epilepsy preceded by febrile seizures. |
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| المؤلفون: | Song W; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Bian WJ; Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China., Li H; Department of Neurology, The Guangdong 999 Brain Hospital, Guangzhou, Guangdong, China., Guo QH; Department of Pediatrics, The Second Hospital of Shandong University, Jinan, Shandong, China., Wang J; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Tang B; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Zhang JY; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Wei W; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Liu XR; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Liao WP; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China., Li B; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China henachilli@163.com lcmlibin@163.com., He N; Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China henachilli@163.com lcmlibin@163.com. |
| المصدر: | Journal of medical genetics [J Med Genet] 2024 Aug 29; Vol. 61 (9), pp. 895-903. Date of Electronic Publication: 2024 Aug 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: British Medical Association Country of Publication: England NLM ID: 2985087R Publication Model: Electronic Cited Medium: Internet ISSN: 1468-6244 (Electronic) Linking ISSN: 00222593 NLM ISO Abbreviation: J Med Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : British Medical Association |
| مواضيع طبية MeSH: | Seizures, Febrile*/genetics , Epilepsy, Generalized*/genetics , Interferon-Induced Helicase, IFIH1*/genetics , Mutation, Missense*/genetics , Genetic Association Studies* , Exome Sequencing*, Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Genetic Predisposition to Disease ; Adult ; Phenotype |
| مستخلص: | Background: IFIH1 variants have been reported to be associated with immune-related disorders with/without seizures. It is unknown whether IFIH1 variants are associated with common epilepsy without acquired causes and the mechanism underlying phenotypic variation remains elusive. Methods: Trio-based whole-exome sequencing was performed on patients with febrile seizures or epilepsy with antecedent febrile seizures. Previously reported variants were systematically reviewed to investigate genotype-phenotype associations. Results: Two de novo heterozygous and three biallelic missense variants were identified in five patients with generalised epilepsy with antecedent febrile seizures. The variants were predicted to be damaging by in silico tools and were associated with hydrogen bonding changes to neighbouring amino acids or decreased protein stability. Patients exhibited an early onset age and became seizure-free with favourable outcome. Further analysis revealed that de novo missense variants located in the Hel region resulted in seizures with multiple neurological abnormalities, while those in the pincer domain or C-terminal domain led to seizures with normal neurodevelopment, suggesting a sub-molecular effect. Biallelic missense variants, which were inherited from unaffected parents and presented low allele frequencies in general populations, were associated with seizures without neurological abnormalities. Truncation variants were related to refractory epilepsy and severe developmental delay, suggesting a genotype-phenotype correlation. IFIH1 is predominantly expressed in the neonatal stage and decreases dramatically in the adulthood, which is consistent with the early onset age and favourable outcome of the patients. Conclusions: IFIH1 variants are potentially associated with generalised epilepsy with antecedent febrile seizures. The sub-molecular implication and genotype-phenotype association help explain phenotype variations of IFIH1 variants. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) |
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| فهرسة مساهمة: | Keywords: epilepsy; genetics |
| المشرفين على المادة: | EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1) EC 3.6.1.- (IFIH1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240704 Date Completed: 20240829 Latest Revision: 20240926 |
| رمز التحديث: | 20240926 |
| مُعرف محوري في PubMed: | PMC11420756 |
| DOI: | 10.1136/jmg-2024-109950 |
| PMID: | 38964834 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1468-6244 |
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| DOI: | 10.1136/jmg-2024-109950 |