Chronic mucocutaneous candidiasis (CMC) characterized by persistent and recurrent
Candida infection of the skin, nails, and the mucosa membranes has been proposed as
the major infectious phenotype in patients with gain-of-function mutation of signal
transducer and activator of transcription 1 (STAT1) 1. However, viral infections caused
mostly by herpesviruses, and a broad range of autoimmune disorders may also be part
of the clinical phenotype. We report here on a 31 years old female patient suffering
from severe mucosal aphthous mucositis and ulcers and recurrent herpes simplex for
decades. We found a previously unknown heterozygous sequence variant inSTAT1(c.1219C>G;
L407V) affecting the DNA-binding domain of the protein in the patient and her 4 years
old daughter. We found this mutation gain-of-function (GOF) by using immunoblot and
luciferase assays. We detected low proportion of IL-17A-producing CD4+ T cell lymphocytes
by using intracellular staining and flow cytometry. Candida-induced secretion of IL-17A
and IL-22 by mononuclear cells from the patient was markedly decreased compared to
controls. These data suggest that the novel mutant allele may result in impaired differentiation
of CD4+ T cells to CD4+/IL-17+ cells. The clinical phenotype of the disease in this
patient was unique as it was dominated primarily by severe aphthous stomatitis and
ulcerative esophagitis and only partly by typical CMC resulting in diagnostic delay.
We suggest that patients with severe recurrent aphthous stomatitis and esophagitis
should be evaluated forSTAT1GOF mutation. Based on the broad clinical spectrum of
the disease, we also suggest that CMC and CMC disease may not be an appropriate term
to define clinicallySTAT1GOF mutation.
