Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children

Fang, Zhixu; Hong, Siqi; Li, Ting-Song; Wang, Juan; Xie, Lingling; Han, Wei; Jiang, Li

doi:10.1097/wnr.0000000000001259

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…The dietary intervention using ketogenic diet proved successful in three patients, who were rather non-responsive to AEDs. The use of sodium channel blockers proved unsuccessful in over 41% of the patients (62). Sodium channel blockers are being discontinued as a choice of treatment for the management of SCN1A-related seizure disorders due to their proven exacerbating effects in the presence of such mutations.…”

Section: Scn1a: Role In Epilepsy and Epilepsy Managementmentioning

confidence: 99%

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

et al. 2021

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Genetic epilepsy occurs as a result of mutations in either a single gene or an interplay of different genes. These mutations have been detected in ion channel and non-ion channel genes. A noteworthy class of ion channel genes are the voltage gated sodium channels (VGSCs) that play key roles in the depolarization phase of action potentials in neurons. Of huge significance are SCN1A, SCN1B, SCN2A, SCN3A, and SCN8A genes that are highly expressed in the brain. Genomic studies have revealed inherited and de novo mutations in sodium channels that are linked to different forms of epilepsies. Due to the high frequency of sodium channel mutations in epilepsy, this review discusses the pathogenic mutations in the sodium channel genes that lead to epilepsy. In addition, it explores the functional studies on some known mutations and the clinical significance of VGSC mutations in the medical management of epilepsy. The understanding of these channel mutations may serve as a strong guide in making effective treatment decisions in patient management.

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Section: Scn1a: Role In Epilepsy and Epilepsy Managementmentioning

confidence: 99%

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

et al. 2021

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“…As many as 2,127 diverse variations in the SCN1A have been reported that map to almost every domain of the voltage-gated sodium channel alpha 1 subunit protein, resulting in a large assortment of potential alterations in channel function. Phenotypic variations as the consequence of SCN1A variations depend on a variety of factors including position, type, and the category of functional change induced by variants, as well as the role of other modifier genes and environmental effects ( Meng et al, 2015 ; Fang et al, 2019 ). The main etiology of SCN1A associated epileptic phenotypes is closely related to its functional changes.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Genotypic Characteristics of SCN1A Associated Seizure Diseases

Chen

Fang

Wang

et al. 2022

Front. Mol. Neurosci.

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Although SCN1A variants result in a wide range of phenotypes, genotype-phenotype associations are not well established. We aimed to explore the phenotypic characteristics of SCN1A associated seizure diseases and establish genotype-phenotype correlations. We retrospectively analyzed clinical data and results of genetic testing in 41 patients carrying SCN1A variants. Patients were divided into two groups based on their clinical manifestations: the Dravet Syndrome (DS) and non-DS groups. In the DS group, the age of seizure onset was significantly earlier and ranged from 3 to 11 months, with a median age of 6 months, than in the non-DS group, where it ranged from 7 months to 2 years, with a median age of 10 and a half months. In DS group, onset of seizures in 11 patients was febrile, in seven was afebrile, in two was febrile/afebrile and one patient developed fever post seizure. In the non-DS group, onset in all patients was febrile. While in the DS group, three patients had unilateral clonic seizures at onset, and the rest had generalized or secondary generalized seizures at onset, while in the non-DS group, all patients had generalized or secondary generalized seizures without unilateral clonic seizures. The duration of seizure in the DS group was significantly longer and ranged from 2 to 70 min (median, 20 min), than in the non-DS group where it ranged from 1 to 30 min (median, 5 min). Thirty-one patients harbored de novo variants, and nine patients had inherited variants. Localization of missense variants in the voltage sensor region (S4) or pore-forming region (S5–S6) was seen in seven of the 11 patients in the DS group and seven of the 17 patients in the non-DS group. The phenotypes of SCN1A-related seizure disease were diverse and spread over a continuous spectrum from mild to severe. The phenotypes demonstrate commonalities and individualistic differences and are not solely determined by variant location or type, but also due to functional changes, genetic modifiers as well as other known and unknown factors.

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“…Currently, most of the research on miR-140-5p is focused on oncology. MiR-140-5p has been shown to be a tumor suppressor gene, and its expression is reduced in several cancer types [6][7][8]. In addition, Liang et al reported that miR-140-5p is also a tissue-specific miRNA that is predominantly expressed in brain, bone, muscle, and other specific tissues or organs [18].…”

Section: Discussionmentioning

confidence: 99%

“…A study reported that microRNAs are also linked to morphine tolerance [5]. Moreover, miR-140-5p is expressed at low levels in a variety of cancer tissues, and exerts a vital influence in cancer invasion and metastasis [6][7][8]. However, the influence of miR-140-5p in morphine tolerance and its mechanism have not been reported and are uncertain.…”

Section: Introductionmentioning

confidence: 99%

MiR-140-5p inhibits morphine tolerance in rats by targeting TLR4

Liu¹,

Xiong²

2021

Trop. J. Pharm Res

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Purpose: To determine the influence of miR-140-5p on morphine tolerance in rats.Methods: Sprague-Dawley (SD) rats were randomly divided into morphine tolerance (MT) and saline control (NS) groups, respectively. Rats in MT group were injected with 10 μL (10 μg) morphine twice daily for seven consecutive days while those in NS group were administered the equivalent volume of normal saline. The maximum effect of morphine (MPE) was computed from tail-flick test results. MiR-140-5p mimics and toll-like receptor 4 (TLR4) lentivirus were transfected separately or co-transfected into model rats. MiR-140-5p and TLR4 expression were determined by quantitative real-time polymerase chain reaction (RT-qPCR) or western blotting. Dual-luciferase reporter assay was used to verify the target relationship between miR-140-5p and TLR4.Results: The expression of miR-140-5p was decreased, while the expression of TLR4 increased in morphine-tolerant rats (p < 0.05). TLR4 was a target of miR-140-5p. At 24 and 48 h after injection, MPE clearly increased and TLR4 expression was reduced under miR-140-5p overexpression or TLR4 knockdown (p < 0.05). Moreover, there were no significant changes in MPE or levels of TLR4 when miR-140-5p and TLR4 were co-transfected into morphine-tolerant rats.Conclusion: MiR-140-5p inhibits morphine resistance in rats via targeted regulation of TLR4 expression. These provide a theoretical basis for the clinical management of morphine tolerance.

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Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children

Cited by 11 publications

References 27 publications

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

Phenotypic and Genotypic Characteristics of SCN1A Associated Seizure Diseases

MiR-140-5p inhibits morphine tolerance in rats by targeting TLR4

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