• Journal of Interdisciplinary Genomics
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• 제3권1호
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• pp.13-20
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• 2021

Developmental and epileptic encephalopathies are the most devastating early-onset epilepsies, characterized by early-onset seizures that are often intractable, electroencephalographic abnormalities, developmental delay or regression, and various comorbidities. A large number of underlying genetic variants of developmental and epileptic encephalopathies have been identified over the past few decades. However, the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. This review explores the genetic basis of developmental and epileptic encephalopathies that start within the first year of life, including Ohtahara syndrome, early myoclonic encephalopathy, epilepsy of infancy with migrating focal seizures, infantile spasms, and Dravet syndrome. The purpose of this review is to give an overview and encourage the clinicians to start considering genetic testing as an important investigation along with electroencephalogram for better understanding and management of developmental and epileptic encephalopathies.

• Genes and Genomics
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• 제40권11호
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• pp.1149-1155
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• 2018

Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.