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  1. De-novo mutations and genetic variation in the SCN1A gene in Malaysian patients with generalized epilepsy with febrile seizures plus (GEFS+)
    Tan EH, Razak SA, Abdullah JM, Mohamed Yusoff AA
    Epilepsy Res, 2012 Dec;102(3):210-5.
    PMID: 22944210 DOI: 10.1016/j.eplepsyres.2012.08.004
    Generalized epilepsy with febrile seizures plus (GEFS+) comprises a group of clinically and genetically heterogeneous epilepsy syndrome. Here, we provide the first report of clinical presentation and mutational analysis of SCN1A gene in 36 Malaysian GEFS+ patients. Mutational analysis of SCN1A gene revealed twenty seven sequence variants (missense mutation and silent polymorphism also intronic polymorphism), as well as 2 novel de-novo mutations were found in our patients at coding regions, c.5197A>G (N1733D) and c.4748A>G (H1583R). Our findings provide potential genetic insights into the pathogenesis of GEFS+ in Malaysian populations concerning the SCN1A gene mutations.
    Matched MeSH terms: Seizures, Febrile/genetics*
  2. Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes
    Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC
    Neurol Sci, 2020 Mar;41(3):591-598.
    PMID: 31720899 DOI: 10.1007/s10072-019-04122-9
    INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

    METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

    RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

    CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

    Matched MeSH terms: Seizures, Febrile/genetics*
  3. Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure: a Multicenter Cohort Study and Meta-analysis
    Haerian BS, Baum L, Kwan P, Cherny SS, Shin JG, Kim SE, et al.
    Mol Neurobiol, 2016 10;53(8):5457-67.
    PMID: 26452361 DOI: 10.1007/s12035-015-9457-y
    Gamma-aminobutyric acid receptor (GABA-A) is the most common receptor of fast synaptic inhibition in the human brain. Gamma protein encoded by the GABRG2 gene is one of the subunits of the GABA-A receptor, which plays an essential role in the function of this receptor. Several studies have identified various febrile seizure (FS) and epilepsy risk variants of GABRG2 gene in different populations, but some others did not support these results. The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea. Furthermore, the pooled dataset of these cohorts with previous reports were meta-analyzed for determining the risk effect size of the rs211037 polymorphism on FS and symptomatic epilepsy (SE). The rs211037, rs210987, rs440218, rs2422106, rs211014, and rs401750 polymorphisms were genotyped in the 6442 subjects (1729 epilepsy and 4713 controls). Results of the case-control study showed associations between rs211037 and the risk of SE in the pooled data from all cohorts (T vs. C, p = 3 × 10(-5), and TT vs. CC, p = 2 × 10(-5)) and the risk of partial seizure in the combined data of Malaysia and Hong Kong (both T vs. C and TT vs. CC, p = 2 × 10(-6)). The rs211037-rs210987 and rs2422106-rs211014-rs401750 haplotypes were also associated with susceptibility to SE in Chinese. Meta-analysis of all Asians identified association between rs211037 and FS and SE (T vs. C, p = 4 × 10(-4), and p = 4 × 10(-3), respectively). In conclusion, rs211037 alone may be a risk factor for FS, partial seizure, and SE, and in linkage disequilibrium with rs210987 can contribute to FS and SE in Asians, particularly in Chinese.
    Matched MeSH terms: Seizures, Febrile/genetics*
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