title: Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency.
abstract: Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition.
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium. ana.alvesdemedeiros@uzgent.be.
authors.forename: Ana Karina
authors.initials: AK
authors.lastname: Alves de Medeiros
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lodewick
authors.affiliation: Department of Pediatric Pulmonology and Immunology, Centre for Primary Immune deficiencies, Ghent University Hospital, Ghent, Belgium.|Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Delfien J A
authors.initials: DJ
authors.lastname: Bogaert
authors.affiliation: Department of Pediatric Pulmonology and Immunology, Centre for Primary Immune deficiencies, Ghent University Hospital, Ghent, Belgium.|Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Filomeen
authors.initials: F
authors.lastname: Haerynck
authors.affiliation: Department of Pediatric Pulmonology and Immunology, Centre for Primary Immune deficiencies, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sabine
authors.initials: S
authors.lastname: Van Daele
authors.affiliation: Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.|Laboratory for Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium.|Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Lambrecht
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Bosma
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Laure
authors.initials: L
authors.lastname: Vanderdonckt
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France.|Infectious Diseases Unit, Necker-Enfants Malades Hospital, AP-HP Paris, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France.|Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Migaud
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France.|Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France.|St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.|Pediatric Hematology-Immunology-Rheumatology Unit, AP-HP, Necker Enfants-Malades Hospital, Paris, France.|Howard Hughes Medical Institute, New York, NY, USA.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France.|Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.affiliation: Paris Descartes University, Imagine Institute, Paris, France.|Infectious Diseases Unit, Necker-Enfants Malades Hospital, AP-HP Paris, Paris, France.|Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Brochez
authors.affiliation: Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.|Laboratory for Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
mesh_terms: D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D002175:Candida / Q000254:growth & development / Q000472:pathogenicity; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002648:Child; D003241:Consanguinity; D005260:Female; D015870:Gene Expression; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D000072742:Invasive Fungal Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D013601:T-Lymphocytes; D014005:Tinea / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014249:Trichophyton / Q000254:growth & development / Q000472:pathogenicity; D014421:Turkey; D000097043:Interleukin-22
chemical_list: D053468:CARD Signaling Adaptor Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020381:Interleukin-17; D015850:Interleukin-6; D007378:Interleukins; D000097043:Interleukin-22; C505855:CARD9 protein, human; C508600:IL6 protein, human
keywords: Autosomal recessive CARD9 deficiency; Chronic mucocutaneous candidiasis; Cutaneous and deep dermatophytosis