TACKLING THE HETEROGENEITY IN PATIENTS WITH CHRONIC MUCOCUTANEOUS CANDIDIASIS CAUSED BY MUTATIONS IN THE STAT1 DNA-BINDING DOMAIN

https://cis.confex.com/cis/2013/webprogram/Paper2438.htmlGain-of-function mutations in the coiled coil domain and DNA binding domain (DBD) of STAT1 were identified in AD and sporadic chronic mucocutaneous candidiasis (CMC). We present two patients with sporadic CMC in whom a mutation in the DBD of STAT1 was identified. Patient 1 is a 20-year old man who presented with extensive Candida diaper dermatitis, recurrent oral and esophageal candidiasis and failure to thrive due to "celiac like" disease from birth. At 3y, chest CT showed bronchiectasis. Enamel hypoplasia, thin hair and recurrent aphtosis were also noticed. AIRE and STAT3 mutations were absent. He developed hypothyroidism (hypoT4) at 18y. Extensive immunological work-up demonstrated IgG2-deficiency, polysaccharide antibody deficiency and hyperIgG. The second patient is a 6 y old girl who was diagnosed with CMC at the age of 2 y based on failure to thrive, oral apthosis and Candida oesophagitis. She had no respiratory infections. The finding of thin hair, coarse facial features and delayed eruption of teeth led to the diagnosis of hypoT4. In both patients, a mutation in the DNA binding domain of STAT1 was identified. Nevertheless, their phenotype was different with bronchiectasis versus hypotT4 as the major clinical problem in patient 1 and 2 respectively next to CMC at early age. This heterogeneity is a major pitfall in the diagnosis. (Immunological and genetic data to be presented at the meeting)status: publishe