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目的:研究一例孤独症谱系障碍(autism spectrum disorder，ASD)合并癫痫患儿的基因变异情况，并探讨其可能的致病机制。方法:收集并评估该患儿的临床资料，应用全外显子测序技术检测患儿及其父母的基因变异位点并筛查致病候选基因，以Sanger法对测序结果进行验证，PolyPhen2对变异结果进行功能预测。应用qPCR研究变异基因在正常人和孤独症谱系障碍患者的表达差异以及该基因在小鼠不同组织的表达差异。结果:先证者系n SIK3基因(Chr11 q23.3，NM_025164.6)存在复合杂合变异，即包含一个遗传自父亲的错义变异[c.1295A>G(p.N432S)]和一个遗传自母亲的缺失变异[c.2389_2391del(p.797del)]。两个变异位点均具有高度保守性，其中PolyPhen2预测c.1295A>G(p.N432S)有害。与母亲相比，先证者与其父亲外周血n SIK3 mRNA表达显著下降；与正常同龄人相比，先证者以及确诊的另外两例孤独症谱系障碍患者外周血n SIK3也明显较低。此外，对小鼠的研究发现，n Sik3基因在大脑中有较高的表达水平。n 结论:SIK3基因变异与ASD有一定关联，具体机制有待进一步研究，可能与脑内脂质代谢受有关。n “,”Objective:To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism.Methods:Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene .Results:The proband carried a compound heterozygous mutation in the n SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c. 1295A>G(p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G[p.N432S]) to be harmful. Compared to the mother, expression ofn SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, n SIK3expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that n Sik3 gene has a marked higher level of expression in the brain.n Conclusion:The n SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.n