CMC, familial Typ 9 B37.-

Very rare (only a few cases have been described worldwide) selective immunodeficiency leading to the clinical picture of chronic mucocutaneous candidiasis (CMC, familial type 9; CANDF9) is caused by a homozygous mutation in the IL17RC gene (610925) on chromosome 3p25. The inheritance pattern of CANDF9 in the families reported by Ling et al. (2015) corresponded to an autosomal recessive inheritance.

Ho et al. (2010) found in animal experiments that Il17rc-null mice showed a dramatic increase in fungal load in the oral cavity after infection with Candida albicans compared with wild-type mice. The results suggest that IL17RC plays an important role in IL17 signaling and in mediating host defense against C. albicans.

Ling et al (2015) reported three unrelated patients with isolated recurrent chronic mucocutaneous candidiasis infections from early childhood. Symptoms included chronic and recurrent oral thrush and impetigo, sometimes with nail involvement. None of the patients had recurrent viral or bacterial infections or other fungal infections. A detailed immunologic examination was normal in all patients, showing normal B-, T-, and NK-cell function and normal production of IL17A (603149). In three unrelated patients with CANDF9, Ling et al. (2015) identified three different homozygous truncating mutations in the IL17RC gene (610925.0001-610925.0003). The mutations found by whole-exome sequencing occurred in families segregated with the disorder. Patient fibroblasts showed decreased IL17RC mRNA levels compared with controls. Patient fibroblasts showed no cytokine response to IL17A and IL17F (606496) homodimers and heterodimers but responded normally to IL17E (IL25; 605658).