CMC is characterized by persistent or recurrent fungal infections of the mucosa, skin, and nails, which can be isolated or associated with other autoimmune disorders and endocrinopathies. Outside of AIRE defects associated with APECED, commercially-available testing for gene mutations associated with CMC are not available. In one cohort with likely autosomal dominant CMC and normal AIRE analysis, we aimed to identify the genetic mutation predisposing to this disorder.
We identified a family affected by CMC, autoimmune disorders, and endocrinopathies with a family history suggestive of autosomal dominant inheritance. We obtained DNA samples under an IRB-approved protocol from 3 affected siblings and 2 unaffected family members. We amplified individual exons of seven genes (CARD9, STAT1, dectin-1, IL-17F, IL-17RA, PTPN22, and TLR3) previously identified to harbor mutations associated with specific CMC phenotypes. Amplified exons were analyzed by DNA sequencing for SNPs.
No subjects in this cohort had mutations in the previously identified exons in CARD9, STAT1, dectin-1, IL-17F, or IL-17RA. One affected subject had a single nucleotide mutation in the PTPN22 gene (R620W). All subjects (affected and unaffected) were found to carry the TLR3 L412F mutant.
All subjects in this cohort had TLR3 L412F, including those without CMC. Activation of TLR3 may be required for the suppression of autoimmunity, which may account for the prevalence of autoimmune endocrinopathies in this family. The PTPN22 R620W variant that was found in only one affected subject but not in other affected members. Additional gene mutations may contribute to autosomal dominant CMC.
Journal of Allergy and Clinical Immunology, Vol. 131, Issue 2, AB153
- AAAAI 2013 (69th)