Chronic mucocutaneous candidiasis in children with STAT1 gene mutations

• Olga P. Kozlova
• Evgeny N. Suspitsin
• Ekaterina V. Frolova
• Tatiyana S. Bogomolova
• Evgeniia B. Milner
• Nadejda V. Shabashova
• Nikolay N. Klimko

Abstract

Purpose. The analysis of clinical features of chronic mucocutaneous candidiasis (CMC) for children with mutations in the STAT1 gene mutations.

Material and methods. The retrospective and prospective analysis of the clinical course of chronic mucocutaneous candidiasis was carried out according to the story cases of observed patients, depending on mutations in the STAT1 gene. Molecular genetic studies were carried out using multigene target sequencing (MiSeq, Illumina, USA).

Results. 6 inpatient and outpatient medical records containing the established diagnosis: primary immunodeficiency state, chronic candidiasis of the skin and mucous membranes associated with a mutation in the STAT1 gene. All patients were revealed autosomal dominant mutations of the STAT1 gene, mainly in the CC domain: M202I, M202V (2 cases), R274Q and 2 new, previously unidentified according to the literature data: Q284R (2011) and D171N (2017). The course of CMC was spontaneously recurrent (>4 times per year) without significant triggers in all patients. Candida albicans was isolated from all patients, resistance to fluconazole and voriconazole in vitro – in 2 patients. All patients had bacterial pneumonia at different periods of their lives, a patient with the D171N mutation developed abscesses of soft tissues and lymph nodes. All patients had systemic or atypical viral infections, including those of the skin and mucous. Lymphopenia was noted at 2 patients (median СD4 – 0.5965 × 10⁹/l). Patients with mutant alleles M202I, M202V, R274Q have no endocrine system lesions yet. A patient with D171N mutant allele was diagnosed with hypoparathyroidism, hypothyroidism, and diabetes mellitus type 1.

Conclusion. Various mutations in the same gene may be associated with different clinical manifestations of chronic mucocutaneous candidiasis, which must be taken into account to optimize the treatment of such patients, including when prescribing antimycotic therapy.

Keywords:chronic mucocutaneous candidiasis; mutations; signal transducer and activator of transcription (STAT); Candida

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