摘要目的:探讨1个进行性家族性肝内胆汁淤积症(PFIC)家系的临床及遗传学特征，探讨其临床表型与基因型的相关性。方法:选取2023年新乡市中心医院确诊的1例PFIC患者作为研究对象，对其进行腹部磁共振成像以及无痛胃镜检查。采集患者及其父母的外周血样，提取基因组DNA进行家系全外显子组测序(trio-WES)。对候选变异进行Sanger测序家系验证。本研究通过了本院医学伦理委员会的审查(批准号：2023-241)。结果:磁共振成像检查显示患者肝、脾明显增大；胃镜检查发现存在毛细血管扩张；WES检测显示患者 ATP8B1基因第16外显子存在c.1710_1711insCCTC(p.A571Pfs*12)杂合移码变异，第24外显子存在c.2989G>A(p.V997M)杂合错义变异，二者分别遗传自其父亲和母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南分别判定为致病性(PVS1＋PM2_Supporting＋PM3＋PP1)和可能致病性(PM2_Supporting＋PM3＋PP1)。 结论:WES检测能够快速、准确地明确患者的遗传学病因，为临床决策提供参考。致病变异的检出为临床诊断提供了依据，丰富了 ATP8B1基因的变异谱。

abstractsObjective:To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation.Methods:A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241).Results:MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c. 1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c. 2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP1) and likely pathogenic (PM2_Supporting+ PM3+ PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Conclusion:WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.