CASE REPORT article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1528844
Pediatric CNS-isolated Hemophagocytic Lymphohistiocytosis Secondary to Uniparental Disomy of PRF1 Mutation
Provisionally accepted
- The Affiliated Hospital of Qingdao University, Qingdao, China
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Background: Central nervous system-isolated hemophagocytic lymphohistiocytosis (CNS-HLH) is a rare disease caused by mutations in several genes. Methods: Clinical information was obtained from medical records. Genetic analyses were performed using whole-exome sequencing (WES). NK cell function testing, Granzyme B staining, perforin staining, CD107a mobilization, and soluble CD25 levels were determined. Results: We report the case of a 5-year-old girl who presented with involuntary movements, an unsteady gait, and a progressively irritable temper. Cranial MRI revealed bilateral multifocal white matter abnormalities. The patient harbored a homozygous missense mutation in the PRF1 gene (NM_001083116.3), c.1349C > T (p.Thr450Met), which is a maternal uniparental disomy. Based on the phenotype and absence of perforin expression, the patient was diagnosed with CNS-HLH. Conclusion: We report a highly unusual case of CNS-HLH diagnosed by uniparental disomy of a PRF1 mutation. Exome sequencing should be considered in patients with chronic or recurrent brain inflammation who show partial or no response to conventional treatment regimens.
Keywords: Central Nervous System, hemophagocytic lympho-histiocytosis, PRF1 gene, Uniparental Disomy, pediatric
Received: 12 Dec 2024; Accepted: 07 Jul 2025.
Copyright: © 2025 Xue, Song, Zhao, Yang, Li, Yi, Liu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ying Zhang, The Affiliated Hospital of Qingdao University, Qingdao, China
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