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目的:报告1个携带n KIF1A基因错义变异的孤独症谱系障碍核心家系，并分析n KIF1A基因的致病变异及其表达蛋白结构。n 方法:提取患儿及其双亲外周血DNA，利用全外显子组测序(whole exome sequencing，WES)技术进行测序，并应用Sanger测序法进行验证。对可疑变异分别用SIFT、PolyPhen-2、Mutation Taster和CADD生物信息学软件分析变异的有害性和保守性；用人脑转录组学(human brain transcriptome，HBT)数据库分析n KIF1A基因在脑内的表达情况；进一步分别用PredictProtein和SWISS-MODEL来预测KIF1A野生型蛋白和变异型蛋白的二级结构和三级结构；用PyMOL V2.4来考察蛋白变异后氢键连接的改变。n 结果:WES测序结果显示患儿n KIF1A基因存在c.664A>C (p.Asn222His)错义变异，且该变异在中国人群中未见报道。有害性预测结果均提示该变异为有害变异。分析该基因在脑内的表达水平，发现其在胚胎发育阶段、各脑区均广泛表达。分析变异后的蛋白结构，发现该错义变异会导致蛋白二级结构中的α螺旋、β折叠和蛋白结合域等结构的诸多改变，氢键连接及空间结构也会发生改变，从而使原有的生物学功能改变。n 结论:KIF1A基因可能是孤独症谱系障碍的风险基因。n “,”Objective:To analyze the pathogenic variants of the n KIF1A gene and its corresponding protein structure in an autism spectrum disorder(ASD) family trio carrying harmful missense variants in the n KIF1A gene.n Methods:The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the n KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.n Results:The WES sequencing revealed a missense variant c. 664A>C (p.Asn222His) in the child’sn KIF1A gene, and this variant was a n de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of n KIF1A gene in the brain. It is found that n KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of n KIF1A will cause many changes in the secondary structure of protein, such as α-helix, β-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.n Conclusion:The n KIF1A gene may be a risk gene for ASD.n