CARD9 Mutations in Patients with Fungal Infections: A Comprehensive Literature Review

CARD9 deficiency is characterized by predisposing to increased susceptibility to fungal infections, particularly invasive fungi and dermatophytes. In recent years, the incidence of fungal infections in patients with CARD9 deficiency is on the rise, and the types of fungal pathogens have become increasingly diverse. In addition, most of CARD9 deficiency patients with fungal disease were prone to recurrence and resistant to antifungal agents, which pose significant challenges to treatment. To investigate the association between CARD9 mutations and fungal infections, we conducted a systematic analysis of published case reports involving 102 CARD9 deficient patients with fungal infections. In this study, the main fungal infections in these patients were candidiasis (34.3%), dermatophytosis (27.5%) and phaeohyphomycosis (23.5%). The main disease-causing fungi were Candida species (36.3%) and Trichophyton species (18.6%). 43 different genetic alterations in the CARD9 gene were identified and the three most frequent mutations were D274fsX60 (21.6%), Q289X (17.7%) and Q295X (12.8%). Our analysis revealed significant geographic variations in the frequency and distribution of CARD9 mutations. In addition, the Q289X and D274fsX60 were predisposed to dermatophytosis and phaeohyphomycosis, respectively. These findings enhance our understanding of the molecular mechanism underlying infection susceptibility in patients with CARD9 deficiency.