Candidiasis, Familial, 9

A number sign (#) is used with this entry because of evidence that familial candidiasis-9 (CANDF9) is caused by homozygous mutation in the IL17RC gene (610925) on chromosome 3p25.

For a general description and a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580).

Clinical Features

Ling et al. (2015) reported 3 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. Detailed immunologic work-up was normal in all patients, showing normal B-, T-, and NK-cell function and production of normal levels of IL17A (603149).

Inheritance

The transmission pattern of CANDF9 in the families reported by Ling et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 3 unrelated patients with CANDF9, Ling et al. (2015) identified 3 different homozygous truncating mutations in the IL17RC gene (610925.0001-610925.0003). The mutations, which were found by whole-exome sequencing, segregated with the disorder in the families. Patient fibroblasts showed decreased levels of IL17RC mRNA compared to controls, and HEK293T cells transfected with the mutations showed absence of IL17RC membrane expression. Patient fibroblasts showed no cytokine response to IL17A and IL17F (606496) homo- and heterodimers, but response to IL17E (IL25; 605658) was normal. Whole blood and monocytes derived from the patients showed normal cytokine responses to fungal compounds.

Animal Model

Ho et al. (2010) found that Il17rc-null mice showed a dramatic increase in fungal burden in the oral cavity after infection with Candida albicans compared to wildtype or heterozygous mice. The findings suggested that IL17RC plays an important role in IL17 signaling and in mediating host defense against C. albicans.