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Updated: Jan 16, 2026
Generation of Fluorescent Protein Fusions in Candida Species
Published on: March 4, 2017
A Child with Chronic Mucocutaneous Candidiasis Harbors a Novel Gain-of-Function Mutation in STAT1
Yang Xiang1, Shuo Sun2, Hong Wang2
1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250000, Shandong Province, P.R. China.
Objective:
Germline heterozygous gain-of-function (GOF) mutations in STAT1 impair IL-17-mediated immunity, resulting in carriers' susceptibility to chronic mucocutaneous candidiasis (CMC). JAK inhibitors have shown therapeutic effectiveness in patients with STAT1-GOF mutations.
Methods:
The mutation was detected using whole-exome sequencing (WES) and confirmed by Sanger sequencing. The functional impact of the mutation was verified by luciferase reporter assay. The phosphorylation level of STAT1 in patient cells, the phenotyping of leukocyte subtypes, and serum cytokine levels were determined by flow cytometry.
Results:
The patient with CMC harbors a heterozygous missense mutation in STAT1 (c.1078G > C, p.V360L). This mutation was functionally validated as a GOF mutation based on functional analysis of the variant and enhanced phosphorylation upon IFN-γ stimulation in the patient's cells. Additionally, the patient demonstrated a decreased proportion of CD4 + T cells, NK cells, and Th17 cells. Flow cytometry analysis revealed a significant decrease in the expression of IL-17 A in CD4 + T cells from the patient. Serological test results showed that the patient's IgM level was decreased, while the levels of IL-2, IL-5, IL-6 and TNF-α were elevated. Topical application of ruxolitinib demonstrated therapeutic efficacy.
Conclusions:
The present study reports a pediatric patient with CMC who carries a novel GOF mutation in STAT1. This mutation may impair IL-17 immunity, which could potentially increase the patient's susceptibility to CMC. However, further research is needed to elucidate the underlying mechanism. Although ruxolitinib shows potential as a therapeutic option for CMC, its clinical efficacy requires further validation through experimental studies and long-term patient follow-up.
Insights
A novel STAT1 (Signal Transducer and Activator of Transcription 1) gain-of-function mutation caused chronic mucocutaneous candidiasis (CMC) in a pediatric patient. JAK inhibitors like ruxolitinib show promise for treating this condition.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- Germline heterozygous gain-of-function (GOF) mutations in STAT1 (Signal Transducer and Activator of Transcription 1) impair IL-17-mediated immunity.
- This impairment leads to increased susceptibility to chronic mucocutaneous candidiasis (CMC).
- JAK inhibitors have demonstrated therapeutic benefits in managing STAT1-GOF mutations.
Purpose of the Study:
- To identify and characterize a novel STAT1 mutation in a pediatric patient with CMC.
- To investigate the functional impact of the identified mutation on immune responses.
- To evaluate the therapeutic potential of JAK inhibitors in this context.
Main Methods:
- Whole-exome sequencing (WES) and Sanger sequencing were used for mutation detection.
- Luciferase reporter assays validated the functional impact of the STAT1 mutation.
- Flow cytometry assessed STAT1 phosphorylation, leukocyte subset phenotyping, and cytokine expression (e.g., IL-17A).
Main Results:
- A novel heterozygous missense mutation (c.1078G>C, p.V360L) in STAT1 was identified in the patient.
- Functional analysis confirmed the mutation as a gain-of-function variant with enhanced STAT1 phosphorylation.
- The patient exhibited reduced CD4+ T cells, NK cells, and Th17 cells, with decreased IL-17A expression. Elevated IgM and specific cytokine levels were also observed.
- Topical ruxolitinib treatment demonstrated therapeutic efficacy.
Conclusions:
- A novel STAT1 GOF mutation is associated with CMC in a pediatric patient, potentially by impairing IL-17 immunity.
- Further research is required to fully elucidate the mechanistic link between this mutation and CMC.
- Ruxolitinib presents a potential therapeutic strategy for CMC, warranting further clinical validation.
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