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Mutations Affect Susceptibility to Fungal Infection

Mutations in the coiled-coil domain of STAT1 found in patients with mucocutaneous candidiasis

WEDNESDAY, June 29 (HealthDay News) -- In patients with autosomal dominant chronic mucocutaneous candidiasis (CMC), mutations in signal transducer and activator of transcription 1 (STAT1) may be associated with increased susceptibility to fungal infections, according to a study published online June 29 in the New England Journal of Medicine.

Frank L. van de Veerdonk, M.D., Ph.D., from the Radboud University Nijmegen Medical Center in the Netherlands, and colleagues analyzed the genetic cause of susceptibility to mucocutaneous fungal infection in 14 patients from five families with autosomal dominant CMC. The investigators selected 100 genes most likely to contain a genetic defect by incubating peripheral-blood mononuclear cells of the participants with different combinations of stimuli. Mutations were identified by array-based sequence capture assay, followed by next-generation sequencing.

The investigators identified poor production of interferon-γ, interleukin-17, and interleukin-22 in the mononuclear cells of the affected patients. Heterozygous missense mutations were identified in the DNA sequence encoding the coiled-coil (CC) domain of STAT1 in the patients, which led to defective responses in type-1 and type-17 helper T cells (Th1 and Th17). In these patients, interferon-γ receptor pathways remained intact.

"Mutations in the CC domain of STAT1 underlie autosomal dominant CMC and lead to defective Th1 and Th17 responses, which may explain the increased susceptibility to fungal infection," the authors write.

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