目的 鉴定导致1例进行性家族性肝内胆汁淤积8（PFIC8）患儿的KIF12基因变异及其对功能的影响。方法 分析1例PFIC8患儿的临床资料，对患儿及其父母进行全外显子组测序，变异用一代测序进行验证。通过免疫荧光染色、细胞模型、实时定量聚合酶链式反应和蛋白质免疫印迹反应研究变异对基因功能的影响。同时对已报道的17例PFIC8患儿的临床资料和基因变异进行文献复习。结果 患儿，男，1个月14天，临床表现以发热和黄疸为主。全外显子组测序发现，患儿的KIF12基因存在c.539G>A+c.928C>T复合杂合突变，此前未见报道。免疫荧光结果显示患儿肝细胞的KIF12蛋白的细胞内定位发生改变。在293T细胞中，c.539A、c.928T和c.539A+c.928T均可以使KIF12的mRNA表达减少，c.928T和c.539A+c.928T可使KIF12的蛋白水平表达降低（P<0.05）。文献回顾显示，已有7个KIF12的纯合突变和1个复合杂合突变（c.538C>T+c.539G>A）被报道。在已报道的病例中，KIF12的突变类型和PFIC8患儿的肝外临床表型无关。结论 在1例PFIC8患儿中发现1种新的KIF12复合杂合突变。在已发现的9个突变中，其类型与PFIC8肝外临床表型可能无关。

Objective To identify KIF12 mutation in an infant with progressive familial intrahepatic cholestasis 8 (PFIC8) and to explore the functional consequences of the mutation. Methods The clinical data of the infant with PFIC8 were analyzed, and whole exome sequencing was conducted on the patient and his parents, and the variation was verified by Sanger sequencing. Immunofluorescence staining, cell phenotyping, qPCR and Western blotting were utilized to investigate the effect of the causative mutations on the gene functions. At the same time, the clinical data and gene variation of 17 reported PFIC8 patients were reviewed. Results The proband, a male infant aged one month and 14 days, exhibited symptoms of fever and jaundice. Whole exome sequencing showed that the KIF12 gene of the patient had a compound heterozygous mutation of c.539G>A+c.928C>T, which had not been reported before. Immunofluorescence staining of liver sections from the patient suggested that the mutation altered the subcellular localization of KIF12 protein within hepatocytes. In 293 T cells, phenotyping of the mutants revealed that c.539A, c.928T and c.539A+c.928T resulted in decreased mRNA levels of KIF12, while c.928T and c.539A+c.928T reduced the protein expression levels of KIF12. A review of the literature revealed seven single site mutations of KIF12 and a compound heterozygous mutation (c.538C>T+c.539G>A) that have been reported. Existing data indicated that the types of KIF12 mutations were not correlated with the extrahepatic clinical phenotypes of PFIC8 patients. Conclusions A novel compound heterozygous mutation was identified in an infant with PFIC8. Among the nine KIF12 mutations identified to date, the mutation types were not associated with the extrahepatic clinical phenotypes of PFIC8.