1. A mutation in KCNT1 gene causing developmental and epileptic encephalopathy in a Vietnamese pediatric patient
Main Article Content
Abstract
Combining clinical diagnosis with genetic analysis is considered necessary to reach accurate conclusions and select appropriate treatments for developmental and epileptic encephalopathy. Whole exome sequencing is a method of next-generation sequencing that provides information about protein-coding regions to identify disease-causing mutations. This study utilized whole exome sequencing for a Vietnamese female pediatric patient suspected of having developmental and epileptic encephalopathy at Children's Hospital 2. Through data screening, we identified a missense mutation in the conserved position of the KCNT1 gene, p.Ala934Thr. This mutation is classified as pathogenic and causes structural changes in the protein, affecting potassium channel activity and causing developmental and epileptic encephalopathy. This is a new insight into the disease-causing mechanism of the KCNT1 gene mutation, providing a basis for accurate diagnosis and appropriate treatment.
Article Details
Keywords
Epilepsy, mutation, exome, KCNT1, Developmental and epileptic encephalopathy
References
2. Raga S, Specchio N, Rheims S, Wilmshurst JM. Developmental and epileptic encephalopathies: recognition and approaches to care. Epileptic Disorders. 2021;23(1):40-52. doi:https://doi.org/10.1684/epd.2021.1244
3. Yang H, Yang X, Cai F, et al. Analysis of clinical phenotypic and genotypic spectra in 36 children patients with Epilepsy of Infancy with Migrating Focal Seizures. Scientific Reports. 2022;12(1):1-10.
4. Choi M, Scholl UI, Ji W, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proceedings of the National Academy of Sciences. 2009;106(45):19096-19101. doi:10.1 073/pnas.0910672106
5. Ng SB, Turner EH, Robertson PD, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):272-276. doi:10.1038/nature0 8250
6. Dillon OJ, Lunke S, Stark Z, et al. Exome sequencing has higher diagnostic yield compared to simulated disease-specific panels in children with suspected monogenic disorders. European Journal of Human Genetics. 2018;26(5):644-651. doi:10.1038/s41431-018-0099-1
7. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.
8. Cole BA, Clapcote SJ, Muench SP, et al. Targeting KNa1.1 channels in KCNT1-associated epilepsy. Trends in Pharmacological Sciences. 2021;42(8):700-713. doi:https://doi.org/10.1016/j.tips.2021.05.003
9. Wilson CS, Mongin AA. The signaling role for chloride in the bidirectional communication between neurons and astrocytes. Neuroscience Letters. 2019;689:33-44. doi:https://doi.org/10. 1016/j.neulet.2018.01.012
10. Amy M, Umesh N, Sony M, et al. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy. Neurology. 2018;90(1):e55. doi:10.1212/WNL. 0000000000004762
11. Numis AL, Nair U, Datta AN, et al. Lack of response to quinidine in KCNT1-related neonatal epilepsy. Epilepsia. 2018;59(10):1889-1898. doi:https://doi.org/10.1111/epi.14551
12. Quraishi IH, Stern S, Mangan KP, et al. An epilepsy-associated KCNT1 mutation enhances excitability of human iPSC-derived neurons by increasing slack KNa currents. Journal of Neuroscience. 2019;39(37):7438-7449.
13. Giulia B, Nicole C, Mathieu K, et al. Epilepsy with migrating focal seizures. Neurology Genetics. 2019;5(6):e363. doi:10.1212/NXG.0000000000000363
14. Bonardi CM, Heyne HO, Fiannacca M, et al. KCNT1-related epilepsies and epileptic encephalopathies: phenotypic and mutational spectrum. Brain. 2021;144(12):3635-3650. doi:10.1093/brain/awab219
15. Barcia G, Fleming MR, Deligniere A, et al. De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy. Nature Genetics. 2012;44(11):1255-1259. doi:10.1038/ng.2441