摘要目的:探讨1例家族性噬血细胞性淋巴组织细胞增生症(FHL)患者的遗传学病因，并对其家系成员进行基因变异分析。方法:选取2021年8月3日因"发热7 +h"就诊于厦门大学附属东方医院(联勤保障部队第九〇〇医院)的1例家族性FHL男性患者(出生35日)作为研究对象。应用全外显子组测序(WES)技术对先证者及其父母进行致病变异筛查。根据先证者的临床表型，确定候选变异，并通过Sanger测序进行验证。 结果:WES结果显示先证者存在 PRF1：c.67_71delinsGCCC及c．65delC变异，Sanger测序证实二者分别遗传自其母亲和父亲。其中c.67_71delinsGCCC为未见报道的新变异。根据美国医学遗传学与基因组学学会相关指南判定为致病性变异(PVS1+PM2_Supporting+PM3+PP4)，c.65delC为已知的致病变异(PVS1+PM2_Supporting +PM3_Strong+PP4)。 结论:PRF1基因c.67_71delinsGCCC及c.65delC复合杂合变异可能是该噬血细胞性淋巴组织细胞增生症患者的遗传学病因。新变异的检出拓展了 PRF1基因的变异谱。

abstractsObjective:To explore the genetic basis for a patient with Familial hemophagocytic lymphohistiocytosis(FHL).Methods:A 35-day-old male infant who was admitted to the Oriental Hospital Affiliated to Xiamen University on August 3, 2021 due to fever for over 7 hours was selected as the study subject. Whole exome sequencing (WES) was carried out for the proband and his parents, and candidate variants were selected based on the clinical phenotypes of the proband and confirmed by Sanger sequencing.Results:WES and Sanger sequencing results revealed that the proband had harbored compound heterozygous variants c. 67_71delinsGCCC and c. 65delC of the PRF1 gene, which were respectively inherited from his mother and father. The c. 67_71delinsGCCC variant was unreported previously. Based on the guidelines of American College of Medical Genetics and Genomics and clinical manifestations, it was classified as pathogenic (PVS1+ PM2_Supporting+ PM3+ PP4). c. 65delC was a known pathogenic variant (PVS1+ PM2_Supporting + PM3_Strong+ PP4). Conclusion:The compound heterozygous variants of c.67_71delinsGCCC and c. 65delC of the PRF1 gene probably underlay the disease in the proband. The identification of the novel variant has expanded the mutational spectrum of the PRF1 gene.