Autosomal recessive deficiency in the caspase recruitment domain containing protein 9 (CARD9) results in susceptibility to fungal infections. In the last decade, infections associated with CARD9 deficiency are more reported due to the advent of genome sequencing. The aim of this study was to evaluate the frequency, geographic distribution and nature of mutations in patients with CARD9 deficiency. We identified 60 patients with 24 mutations and different fungal infections. The presence of the homozygous (HMZ) p.Q295X (c.883C > T) and HMZ p.Q289X (c.865C > T) mutations were associated with an elevated risk of candidiasis (OR: 1.6; 95% CI: 1.18–2.15; p = 0.004) and dermatophytosis (OR: 1.85; 95% CI: 1.47–2.37; p < 0.001), respectively. The geographical distribution differed, showing that the main mutations in African patients were different Asian patients; HMZ p.Q289X (c.865C > T) and HMZ p.Q295X (c.865C > T) accounted for 75% and 37.9% of the African and Asian cases, respectively. The spectrum of CARD9 mutations in Asian patients was higher than in African. Asia is the most populous continent in the world and may have a greater genetic burden resulting in more patients with severe fungal infections. The presence of a high diversity of mutations revealing 24 distinct variations among 60 patients emphasize that the unique genetic alteration in CARD9 gene may be associated with certain geographical areas.

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different ascomycete orders. This is particularly the situation with those that have melanized cell walls that cause human and animal disorders [1], such as species of Cladophialophora , Exophiala , Fonsecaea which belong to the order Chaetothyriales [1,2], while hyphomycete Cladosporium spp. and coelomycetes (fungi producing asexual fruit-bodies) are members of the order Dothideales [2]. Cladosporium species and certain coelomycetes are widely distributed in soil, on wood, and plant debris, and are often encountered as plant pathogens [3]. Fast-growing dematiaceous fungi such as Bipolaris , Curvularia , A 27-year-old Iranian, previously healthy male presented with sub-cutaneous necrotic lesions with a localized dermatosis affecting the anterior chest, neck and face. These lesions consisted of singular, well-defi ned verrucous plaques which gradually developed and disseminated over time. The dermatosis was followed by the development of necrotic swollen lesions localized on the hard palate. The patient did not recall any history of trauma or puncture at any of the sites of infection. While histopathological examination of periodic acid-Schiff (PAS) stained material revealed irregular, unbranched, septate hyphae, direct examination (KOH 10%) of lesion samples demonstrated the presence of septate indistinct brownish hyphae. Alternaria malorum was isolated (CBS 126589) and its identity was confi rmed by sequencing of the internal transcribed spacer (ITS rDNA). Since the palate lesion reoccurred after 10 years and the patient ' s condition did not improve with amphotericin B combination therapy, the lesion was surgical excised and he underwent antifungal therapy with amphotericin B and itraconazole. There was no dehiscence or fi stula formation or any evidence of relapse of fungal infection during a one year follow-up and the patient was successfully cured. In vitro antifungal susceptibility tests revealed that the MIC values for those antifungals employed in this case were amphotericin B (0.125 μ g/ml), fl uconazole (32 μ g/ml), itraconazole (0.125 μ g/ml), voriconazole (1 μ g/ml), and posaconazole (0.063 μ g/ml). The MECs for caspofungin and anidulafungin were 0.25 μ g/ml and 0.016 μ g/ml, respectively. However, treatment of A. malorum infections with the latter agents remains to be evaluated.

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