AUTHOR=Martinot Martin , Korganow Anne Sophie , Wald Mathieu , Second Julie , Birckel Elodie , Mahé Antoine , Souply Laurent , Mohseni-Zadeh Mahsa , Droy Laure , Tarabeux Julien , Okada Satoshi , Migaud Mélanie , Puel Anne , Guffroy Aurelien TITLE=Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.760019 DOI=10.3389/fimmu.2021.760019 ISSN=1664-3224 ABSTRACT=Purpose

Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis.

Methods

Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect.

Results

NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement.

Conclusion

We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.