An association analysis at 2q36 reveals a new candidate susceptibility gene for juvenile absence epilepsy and/or absence seizures associated with generalized tonic-clonic seizures

Yalçın, Özlem Çapan; Baykan, Betül; Ağan, Kadriye; Yapıcı, Zühal; Yalcin, Destina; Dizdarer, Gülşen; Türkdoğan, Dilşad; Özkara, Çiğdem; Ünalp, Aycan; Uludüz, Derya; Gül, Günay; Kuşçu, Demet Yandım; Ayta, Semih; Tutkavul, Kemal; Çomu, Sinan; Tatlı, Burak; Meral, Cihan; Bebek, Nerses; Çağlayan, S. Hande

doi:10.1111/j.1528-1167.2010.02970.x

Cited by 5 publications

(4 citation statements)

References 40 publications

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“…Sander et al reported an allelic association with GLU R5 kainate receptor gene (GRIK1 polymorphism), which has a role in excitatory neurotransmission [ 81 ]. Another association study revealed a strong association of a common intronic SNP (rs7588807) in the inhibin alpha precursor gene (INHA) with JAE [ 113 ]. INHA encodes inhibin protein, which inhibits the secretion of follicle-stimulating hormone (FSH), in turn inducing the production of progesterone and estradiol.…”

Section: Genetic Studies Of Common Epilepsiesmentioning

confidence: 99%

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment

Thakran

Guin

Singh

et al. 2020

IJMS

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Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management.

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Section: Genetic Studies Of Common Epilepsiesmentioning

confidence: 99%

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment

Thakran

Guin

Singh

et al. 2020

IJMS

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“…An association study with 205 Turkish IAE patients revealed a strong association of a common SNP (rs7588807) in the inhibin alpha precursor gene (INHA) in 2q36 to JAE and/or to IAE with GTCS. 76 The INHA gene has also been screened through DNA analysis and three potentially damaging mutations have been identified. Inhibin protein, commonly known as a gonadal glycoprotein, inhibits the secretion of follicle-stimulating hormone which in turn induces the production of progesterone and estradiol.…”

Section: Non-ion Channel Genesmentioning

confidence: 99%

Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies

Yalçın

2012

Seizure

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Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants.

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“… 4 AEs are often studied apart, but some investigations show common genetic causality, 5 whereas others identify factors that are not shared. 6 Recurrent microdeletions at 15q11.2, 15q13.3, and 16p13.11 are strongly associated risk factors for GGEs, occurring in 0.5% to 1% of patients. 7 Around 8% of patients with GGE also carry rare gene-disrupting copy number variations (CNVs), with enrichment for genes previously implicated in neurodevelopmental disorders, including deletions of RBFOX1 and NRXN1 .…”

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confidence: 99%

Analysis of rare copy number variation in absence epilepsies

et al. 2016

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Objective:To identify shared genes and pathways between common absence epilepsy (AE) subtypes (childhood absence epilepsy [CAE], juvenile absence epilepsy [JAE], and unclassified absence epilepsy [UAE]) that may indicate common mechanisms for absence seizure generation and potentially a diagnostic continuum.Methods:We used high-density single-nucleotide polymorphism arrays to analyze genome-wide rare copy number variation (CNV) in a cohort of 144 children with AEs (95 CAE, 26 UAE, and 23 JAE).Results:We identified CNVs that are known risk factors for AE in 4 patients, including 3x 15q11.2 deletion. We also expanded the phenotype at 4 regions more commonly identified in other neurodevelopmental disorders: 1p36.33 duplication, 1q21.1 deletion, 22q11.2 duplication, and Xp22.31 deletion and duplication. Fifteen patients (10.5%) were found to carry rare CNVs that disrupt genes associated with neuronal development and function (8 CAE, 2 JAE, and 5 UAE). Four categories of protein are each disrupted by several CNVs: (1) synaptic vesicle membrane or vesicle endocytosis, (2) synaptic cell adhesion, (3) synapse organization and motility via actin, and (4) gap junctions. CNVs within these categories are shared across the AE subtypes.Conclusions:Our results have reinforced the complex and heterogeneous nature of the AEs and their potential for shared genetic mechanisms and have highlighted several pathways that may be important in epileptogenesis of absence seizures.

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An association analysis at 2q36 reveals a new candidate susceptibility gene for juvenile absence epilepsy and/or absence seizures associated with generalized tonic-clonic seizures

Cited by 5 publications

References 40 publications

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment

Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment

Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies

Analysis of rare copy number variation in absence epilepsies

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