Abstract：
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.
摘要：
癫痫性脑病是导致癫痫并引起神经系统疾病的遗传异质性疾病。位于1p34.2染色体上的癫痫阈值2（SZT2）基因编码的蛋白质主要在大脑的顶叶和额叶皮质以及背根神经节中表达。先前在小鼠中的研究表明，该基因的突变可以赋予低癫痫发作阈值，增强癫痫发生，在人类中可能导致面部畸形，智力残疾,癫痫发作和大头畸形。本研究的目的是找出与基因表型相关的新基因或新突变。我们已经确定了一个巨大的血缘关系的沙特家庭隔离发育迟缓，智力残疾,癫痫,高额头和大头畸形。在受影响的家族兄弟姐妹中进行外显子组测序以研究新突变。全外显子组测序数据分析,随后的Sanger测序验证研究证实。我们的结果显示在SZT2基因的外显子67中将保守的甘氨酸残基替换为谷氨酸中的新的纯合突变(c.9368G>A)。在100个无关的健康对照中排除了该突变。该错义变体在文献或变体数据库中尚未被报道为致病性的。总之,此处检测到的纯合SZT2变异可能是进一步解释该沙特家族癫痫和发育迟缓的致病突变.
