Epilepsy-associated genes: an update

Zhang, Meng-Wen; Liang, Xiao-Yu; Wang, Jie; Gao, Liang-Di; Liao, Han-Jun; He, Yun-Hua; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

doi:10.1016/j.seizure.2023.09.021

Cited by 13 publications

(2 citation statements)

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“…With the advancement of next-generation sequencing (NGS) technologies, researchers continue to identify many genes associated with epilepsy ( Ondruskova et al, 2021 ; Zhang et al, 2023 ). However, the current next-generation sequencing (NGS) panels for epilepsy and whole-exome sequencing (WES) testing have a diagnostic yield of 25% and 45%, respectively ( Krey et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Alaamery,

Massadeh,

Aldarwish

et al. 2024

Front. Genet.

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Congenital disorders of glycosylation (CDG) are a group of more than 100 rare genetic disorders characterized by impaired glycosylation of proteins and lipids. The clinical presentation of CDG varies tremendously, from single-organ to multi-organ involvement and from prenatal death to a normal adult phenotype. In this case study, we report a large consanguineous family with multiple children suffering from cerebral palsy, seizure, developmental and epileptic encephalopathy, and global developmental delay. Whole-exome sequencing (WES) analysis revealed a homozygous variant in the UDP-glucose dehydrogenase (UGDH) gene (c.950G>A; p.R317Q) which segregates with the familial phenotype with a plausible autosomal recessive mode of inheritance, indicating a potential disease-causing association. The UGDH gene encodes the UDP-glucose dehydrogenase, a key enzyme in the synthesis of specific extracellular matrix constituents (proteoglycans and glycolipids) involved in neural migration and connectivity during early brain development. Many pathogenic mutations of UGDH have been reported in recent literature works. However, the variant identified in this study has been observed only in the Saudi population (13 families) and not in any other ethnic background, suggesting that it may be an ancient founder mutation.

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Section: Introductionmentioning

confidence: 99%

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Alaamery,

Massadeh,

Aldarwish

et al. 2024

Front. Genet.

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“…Recent advances in genome sequencing identified an increasing number of genes that are associated with epilepsy [2] . According to protein functions, epilepsy-associated genes can be grouped to ion channels, enzymes and enzyme modulators, transports and receptors, and others [3] . Genetic epilepsy is often linked to developmental delay, movement disorder, and other comorbidities [4] .…”

Section: Introductionmentioning

confidence: 99%

Pathogenicity Prediction of GABA_AReceptor Missense Variants

Wang,

Vu,

2023

Preprint

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Variants in the genes encoding the subunits of gamma-aminobutyric acid type A (GABAA) receptors are associated with epilepsy. To date, over 1000 clinical variants have been identified in these genes. However, the majority of these variants lack functional studies and their clinical significance is uncertain although accumulating evidence indicates that proteostasis deficiency is the major disease-causing mechanism for GABAAreceptor variants. Here, we apply two state-of-the-art modeling tools, namely AlphaMissense, which uses an artificial intelligence-based approach based on AlphaFold structures, and Rhapsody, which integrates sequence evolution and known structure-based data, to predict the pathogenicity of saturating missense variants in genes that encode the major subunits of GABAAreceptors in the central nervous system, includingGABRA1,GABRB2,GABRB3, andGABRG2. Our results demonstrate that the predicted pathogenicity correlates well between AlphaMissense and Rhapsody although AlphaMissense tends to generate higher pathogenic probability. Furthermore, almost all annotated pathogenic variants in the ClinVar clinical database are successfully identified from the prediction, whereas uncertain variants from ClinVar partially due to the lack of experimental data are differentiated into different pathogenicity groups. The pathogenicity prediction of GABAAreceptor missense variants provides a resource to the community as well as guidance for future experimental and clinical investigations.

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ARHGAP4 variants are associated with X-linked early-onset temporal lobe epilepsy

Hu,

Song,

Liu

et al. 2024

World J Pediatr

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Epilepsy-associated genes: an update

Cited by 13 publications

References 50 publications

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Pathogenicity Prediction of GABA_AReceptor Missense Variants

ARHGAP4 variants are associated with X-linked early-onset temporal lobe epilepsy

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Epilepsy-associated genes: an update

Cited by 13 publications

References 50 publications

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia

Pathogenicity Prediction of GABAAReceptor Missense Variants

ARHGAP4 variants are associated with X-linked early-onset temporal lobe epilepsy

Contact Info

Product

Resources

About

Pathogenicity Prediction of GABA_AReceptor Missense Variants