RESUMO
PURPOSE: In the past decade, an increasing number of otherwise healthy individuals suffered from invasive fungal infections due to inherited CARD9 mutations. Herein, we present a patient with a homozygous CARD9 mutation who was suffering from localized subcutaneous phaeohyphomycosis caused by the phytopathogenic fungus Pallidocercospora crystallina which has not been reported to cause infections in humans. METHODS: The medical history of our patient was collected. P. crystallina was isolated from the biopsied tissue. To characterize this novel pathogen, the morphology was analyzed, whole-genome sequencing was performed, and the in vivo immune response was explored in mice. Whole-exome sequencing was carried out with samples from the patient's family. Finally, the expression and function of mutated CARD9 were investigated. RESULTS: A dark red plaque was on the patient's left cheek for 16 years and was diagnosed as phaeohyphomycosis due to a P. crystallina infection. Whole-genome sequencing suggested that that this strain had a lower pathogenicity. The in vivo immune response in immunocompetent or immunocompromised mice indicated that P. crystallina could be eradicated within a few weeks. Whole-exome sequencing revealed ahomozygous missense mutation in CARD9 (c.1118G>C p.R373P). The mRNA and protein expression levels were similar among cells carrying homozygous (C/C), heterozygous (G/C), and wild-type (G/G) CARD9 alleles. Compared to PBMCs or neutrophils with heterozygous or wild-type CARD9 alleles, however, PBMCs or neutrophils with homozygous CARD9 alleles showed impaired anti-P. crystallina effects. CONCLUSION: Localized subcutaneous phaeohyphomycosis caused by P. crystallina was reported in a patient with a homozygous CARD9 mutation. Physicians should be aware of the possibility of a CARD9 mutation in seemingly healthy patients with unexplainable phaeohyphomycosis.