CARD9 mutations in patients with fungal infections: An update from the last 5 years

Abstract Background Autosomal recessive deficiency in the caspase recruitment domain‐containing protein 9 (CARD9) is a congenital immunological condition that leads to susceptibility to mucocutaneous and invasive fungal infections. There is growing incidence of fungal infections in patients with CARD9 deficiency, a phenomenon that is increasingly recognised. Objectives This study aimed to assess the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency, based on published papers in the literature until March 2023. Methods We swiftly conducted a study to pinpoint every documented instance of fungal infections arising from CARD9 deficiency. We selected case reports from the databases of PubMed, Embase, Scopus and Google Scholar spanning the period from October 2009 to March 2023. Results We analysed 90 cases of fungal infections and identified 32 mutations in the CARD9 gene. Notably, the homozygous ( HMZ ) p.Q295X ( c.883C > T ) mutation was associated with an increased risk of candidiasis. In contrast, the HMZ p.Q289X ( c.865C > T ) mutation is linked to a higher risk of dermatophytosis. We observed differences in the geographical distribution of these mutations. The primary mutations found in African patients differ from those in Asian patients. Specifically, Asian patients exhibit a broader spectrum of CARD9 mutations than African patients. Conclusions The diversity of mutations observed in the 90 cases revealed 32 distinct variations, emphasising the unique genetic alterations in the CARD9 gene associated with specific geographical areas and the corresponding prevalence of fungal infections.