# Case Report: Pediatric CNS-isolated hemophagocytic lymphohistiocytosis secondary to uniparental disomy of PRF1 mutation

## TL;DR

A 5-year-old girl with rare CNS-isolated hemophagocytic lymphohistiocytosis was found to have a PRF1 gene mutation due to uniparental disomy.

## Contribution

This is the first reported case linking CNS-HLH to a PRF1 mutation via uniparental disomy.

## Key findings

- A homozygous missense mutation in PRF1 (c.1349C > T) was identified in the patient.
- The mutation was confirmed to be maternal uniparental disomy.
- The patient showed absence of perforin expression, supporting the CNS-HLH diagnosis.

## Abstract

Central nervous system-isolated hemophagocytic lymphohistiocytosis (CNS-HLH) is a rare disease caused by mutations in several genes.

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.

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.

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.