CARD9 Mutations in Patients with Invasive Fungal Infections

Homozygous mutations in the Caspase-associated recruitment domain 9 (CARD9) gene increase susceptibility to invasive fungal infections, particularly those caused by Candida species. This study aims to assess the spectrum of CARD9 gene mutations that predispose individuals in the Turkish population, especially children, to invasive fungal infections.

Our study included 30 patients who were admitted to Ege University due to invasive fungal infection or chronic mucocutaneous candidiasis between 2020 and 2023. Demographic and clinical data of the patients were recorded, and a sequence analysis of the CARD9 gene was performed.

The median age of the patients was 1.8 years (interquartile range [IQR]: 11.8). Diagnoses included fungal endocarditis (n = 8, 26.6%), chronic mucocutaneous candidiasis (n = 7,23.3%), central nervous system (CNS) infections (n = 6,20%), candidemia (n = 4,13.3%), fungus ball in the kidney (n = 2, 6.7%), endophthalmitis ( n = 1, 3.3%), concurrent CNS and intra-abdominal infection (n = 1, 3.3%), and concurrent CNS infection and endophthalmitis (n = 1, 3.3%). All 12 exons and exon-intron junctions of the CARD9 (NM_052813.5) gene that encodes the CARD9 protein were analyzed. A disease-causing variant was detected in 2 patients (6.6%). One patient had a Pseudallescheria boydii brain abscess, and the other had an invasive fungal infection confirmed histopathologically.

Among the 30 patients with invasive fungal infections, a disease-causing CARD9 mutation was identified in 2 (6.6%) patients. While CARD9 mutations are known to be associated with invasive candidiasis, this study reports the first pediatric case of P. boydii infection associated with a CARD9 mutation.