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Neurogenetics
Published in John W. Scadding, Nicholas A. Losseff, Clinical Neurology, 2011
Sonia Gandhi, Sarah Tabrizi, Nicholas Wood
There are relatively few single gene disorders that result in inherited forms of epilepsy, and these are usually caused by mutations in ion channels or neurotransmitter genes. For example, severe myoclonic epilepsy of infancy is caused by mutations in the a1 subunit of the sodium channel gene SCN1A. Mutations in the b1 subunit of the sodium channel gene SCN1B may cause generalized epilepsy with febrile seizures-plus (GEFS +). Benign infantile neonatal epilepsy is caused by mutations in the potassium channel genes, KCNQ2 or KCNQ3. Juvenile myoclonic epilepsy has been associated with mutations in the chloride channel gene CLCN2.
Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population
Published in Annals of Medicine, 2022
Mansour A. Alghamdi, Laith N. AL-Eitan, Ashwag Asiri, Doaa M. Rababa’h, Sultan A. Alqahtani, Mohammed S. Aldarami, Manar A. Alsaeedi, Raghad S. Almuidh, Abdulbari A. Alzahrani, Ahmad H. Sakah, Eman Mohamad El Nashar, Mansour Y. Otaif, Nawal F. Abdel Ghaffar
The available data that describe the association between SCN3A variants and epilepsy are limited and few were correlated to focal epilepsy [19]. rs1057518801 and rs1057520753 of SCN3A manifest a gain of function in sodium channels that results in more hyperpolarized potentials and had been linked to early infantile epileptic encephalopathy [20]. SCN1B and SCN2B gene have been associated with GEFS [21,22] and dravet syndrome [13,23]. rs786205830 is a loss of function mutation in the SCN1B gene had been linked to early infantile developmental and epileptic encephalopathy (Aeby et al. 2019). SCN8A has been reported to influence epilepsy at four months of early life and can affect the development. This gene may also enhance several epilepsy syndromes such as Lennox-Gastaut syndrome, West syndrome and epileptic encephalopathies (e.g. Dravet syndrome) [16]. Moreover, SCN8A also related to EIEE and BFIS (Makoff et al. 2009).
Advances in the design and discovery of novel small molecule drugs for the treatment of Dravet Syndrome
Published in Expert Opinion on Drug Discovery, 2021
Barbara Miziak, Stanisław Czuczwar
Another mutation that seems to be connected with DS is the mutation of SCN9A encoding NaV.1.7 [18,19]. This mutation type is directly linked to FS, however, one patient with it also developed DS. As a result, a group of DS patients was examined. In some of them, an additional mutation of SCN9A (the presence of both SCN9A and SCN1A gene mutation) was evident. Interestingly, in the case of three patients from this group no SCN1A gene mutation was found [18]. It is also worth noting that in each case of a gene mutation (both SCN1A and SCN9A) a few variations of such mutation can be distinguished [18,19]. Further studies facilitated the identification of mutations in other genes which occurred individually or were paired with SCN1A gene mutation. Among them SCN1B and SCN2B genes are distinguished, however, their effects on the DS development are doubtful, in particular in the case of SCN2B gene mutation [19–23]. In fact, the current medical literature considers the patients presenting with mutations like for instance STXBP1, different from DS patients and affected by specific epileptic encephalopathies or DEEs. It should be stressed that with the most recent genetic tests such mutations may be encountered in almost all the patients [4].
Unravelling the genetic architecture of autosomal recessive epilepsy in the genomic era
Published in Journal of Neurogenetics, 2018
Jeffrey D. Calhoun, Gemma L. Carvill
As discussed above, de novo models, particularly in the EOEEs have dominated gene discovery in recent years. However, there are a growing number of case reports suggesting that genes originally identified in autosomal dominant (or de novo) epilepsies may also cause epilepsy when pathogenic variants are inherited in an AR manner. For example, SCN1B, encoding the β1 subunit of the voltage-gated sodium channel, was the first gene reported in genetic epilepsy with febrile seizures plus (GEFS+) patients (Wallace et al., 1998). While heterozygous SCN1B variants result in a relatively mild GEFS + phenotype, homozygous variants were later found in patients with the much more severe presentation of EOEE (Ogiwara et al., 2012; Patino et al., 2009). Importantly, transgenic mouse models recapitulate Scn1b-related epilepsy phenotypes. Homozygous Scn1b null mice lacking β1 subunit expression exhibit spontaneous generalized seizures and all mice with this genotype fail to survive to adulthood (Chen et al., 2004). Meanwhile, heterozygous knockin SCN1B-C121W mice are susceptible to hyperthermia-induced seizures, similar to febrile seizures in GEFS+ (Kruger et al., 2016; Wimmer et al., 2010).