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Recurrent fungal infections in a Chinese patient with CARD 9 deficiency and a review of 48 cases
Author(s) -
Quan C.,
Li X.,
Shi R.F.,
Zhao X.Q.,
Xu H.,
Wang B.,
Wang X.P.,
Hu W.G.,
Cao H.,
Zheng J.
Publication year - 2019
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.17092
Subject(s) - candida albicans , medicine , frameshift mutation , peripheral blood mononuclear cell , immunology , trichosporon , nonsense mutation , gastroenterology , biology , mutation , microbiology and biotechnology , missense mutation , gene , yeast , biochemistry , genetics , in vitro
Summary Deficiency of CARD 9 (caspase recruitment domain‐containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans , peripheral blood mononuclear cells of this patient produced less tumour necrosis factor‐α, interferon‐γ and interleukin‐17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD 9. We further performed a review including 48 cases with CARD 9 deficiency. According to the data published previously, CARD 9‐deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL −1 ), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled‐coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).