Vaezi Afsane, Fakhim Hamed, Abtahian Zahra, Khodavaisy Sadegh, Geramishoar Mohsen, Alizadeh Ahad, Meis Jacques F, Badali Hamid
Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Front Microbiol. 2018 Oct 12;9:2434. doi: 10.3389/fmicb.2018.02434. eCollection 2018.
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; = 0.004) and dermatophytosis (OR: 1.85; 95% CI: 1.47-2.37; < 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 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 gene may be associated with certain geographical areas.
含半胱天冬酶募集结构域蛋白9（CARD9）的常染色体隐性缺陷会导致易患真菌感染。在过去十年中，由于基因组测序的出现，与CARD9缺陷相关的感染报告得更多。本研究的目的是评估CARD9缺陷患者中突变的频率、地理分布和性质。我们鉴定了60例有24种突变且患有不同真菌感染的患者。纯合子（HMZ）p.Q295X（c.883C>T）和HMZ p.Q289X（c.865C>T）突变的存在分别与念珠菌病风险升高（比值比：1.6；95%置信区间：1.18 - 2.15；P = 0.004）和皮肤癣菌病风险升高（比值比：1.85；95%置信区间：1.47 - 2.37；P < 0.001）相关。地理分布有所不同，表明非洲患者的主要突变与亚洲患者不同；HMZ p.Q289X（c.865C>T）和HMZ p.Q295X（c.865C>T）分别占非洲和亚洲病例的75%和37.9%。亚洲患者的突变谱比非洲患者的更高。亚洲是世界上人口最多的大陆，可能有更大的遗传负担，导致更多严重真菌感染患者。60例患者中出现24种不同变异的高度多样的突变表明，该基因中的独特基因改变可能与某些地理区域相关。
