title: Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection.
abstract: BACKGROUND
  Exophiala species are mostly responsible for skin infections. Invasive Exophiala dermatitidis disease is a rare and frequently fatal infection, with 42 cases reported. About half of these cases had no known risk factors. Similarly, invasive Exophiala spinifera disease is extremely rare, with only 3 cases reported, all in patients with no known immunodeficiency. Autosomal recessive CARD9 deficiency has recently been reported in otherwise healthy patients with severe fungal diseases caused by Candida species, dermatophytes, or Phialophora verrucosa.
  
  
  METHODS
  We investigated an 8-year-old girl from a nonconsanguineous Angolan kindred, who was born in France and developed disseminated E. dermatitidis disease and a 26 year-old woman from an Iranian consaguineous kindred, who was living in Iran and developed disseminated E. spinifera disease. Both patients were otherwise healthy.
  
  
  RESULTS
  We sequenced CARD9 and found both patients to be homozygous for loss-of-function mutations (R18W and E323del). The first patient had segmental uniparental disomy of chromosome 9, carrying 2 copies of the maternal CARD9 mutated allele.
  
  
  CONCLUSIONS
  These are the first 2 patients with inherited CARD9 deficiency and invasive Exophiala disease to be described. CARD9 deficiency should thus be considered in patients with unexplained invasive Exophiala species disease, even in the absence of other infections.
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Department of Infectious Diseases, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre d'Infectiologie Necker Pasteur.
authors: Fanny
authors: F
authors: Lanternier
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute.
authors: Elisa
authors: E
authors: Barbati
authors: Department of General Pediatrics and Internal Medicine, Robert Debré Hospital, AP-HP University Paris 7 Denis Diderot, Paris Sorbonne Cité
authors: Ulrich
authors: U
authors: Meinzer
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute.
authors: Luyan
authors: L
authors: Liu
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute.
authors: Vincent
authors: V
authors: Pedergnana
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute.
authors: Mélanie
authors: M
authors: Migaud
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit.
authors: Sébastien
authors: S
authors: Héritier
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit.
authors: Maryline
authors: M
authors: Chomton
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit.
authors: Marie-Louise
authors: ML
authors: Frémond
authors: Pediatric Hepatology Unit, DHU Hépatinov, INSERM U757, Paris-Sud 11 University, Bicêtre Hospital, AP-HP.
authors: Emmanuel
authors: E
authors: Gonzales
authors: Pediatric Rheumatology Unit, Bicêtre Hospital, AP-HP, Paris Sud University, CeReMAI.
authors: Caroline
authors: C
authors: Galeotti
authors: Histology, Embryology, and Cytogenetics Unit.
authors: Serge
authors: S
authors: Romana
authors: Pediatric Hepatology Unit, DHU Hépatinov, INSERM U757, Paris-Sud 11 University, Bicêtre Hospital, AP-HP.
authors: Emmanuel
authors: E
authors: Jacquemin
authors: Mycology Laboratory.
authors: Adela
authors: A
authors: Angoulvant
authors: Pediatric Surgery Unit, Bicêtre Hospital, AP-HP, Kremlin Bicêtre.
authors: Valeska
authors: V
authors: Bidault
authors: Pathology Unit.
authors: Danielle
authors: D
authors: Canioni
authors: Department of Pediatrics, Pontoise Hospital, Cergy Pontoise, France, EU.
authors: Julie
authors: J
authors: Lachenaud
authors: Department of Clinical Immunology and Allergy, National Research Institute of Tuberculosis and Lung Diseases, Masih Daneshvari Hospital.
authors: Davood
authors: D
authors: Mansouri
authors: Pediatric Respiratory Disease Research Centre, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences.
authors: Seyed Alireza
authors: SA
authors: Mahdaviani
authors: Department of Medical Mycology and Parasitology, Islamic Azad University Tehran Medical Branch.
authors: Parvaneh
authors: P
authors: Adimi
authors: Department of Clinical Immunology and Allergy, National Research Institute of Tuberculosis and Lung Diseases, Masih Daneshvari Hospital.
authors: Nahal
authors: N
authors: Mansouri
authors: Department of Infectious Disease, Iran University of Medical Sciences, Tehran, Iran.
authors: Mahin
authors: M
authors: Jamshidi
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Microbiology Laboratory Fungal Biology and Pathogenicity, INRA USC 2019, Institut Pasteur.
authors: Marie-Elisabeth
authors: ME
authors: Bougnoux
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York.
authors: Laurent
authors: L
authors: Abel
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Department of Infectious Diseases, Necker-Enfants malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre d'Infectiologie Necker Pasteur Molecular Mycology Unit, National Reference Center for Invasive Mycoses and Antifungals, Institut Pasteur, Paris.
authors: Olivier
authors: O
authors: Lortholary
authors: Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit.
authors: Stéphane
authors: S
authors: Blanche
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York.
authors: Jean-Laurent
authors: JL
authors: Casanova
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute Pediatric Hematology-Immunology Unit Study Center for Primary Immunodeficiencies, Necker-Enfants malades Hospital, AP-HP.
authors: Capucine
authors: C
authors: Picard
authors: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163 Paris Descartes University-Sorbonne Paris Cité, Imagine Institute.
authors: Anne
authors: A
authors: Puel
mesh_terms: D000328:Adult; D000483:Alleles; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency* / Q000235:genetics*; D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005093:Exophiala; D005260:Female; D006720:Homozygote; D006801:Humans; D009154:Mutation / Q000235:genetics; D060446:Phaeohyphomycosis / Q000235:genetics* / Q000382:microbiology
chemical_list: D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human
keywords: Exophiala species; autosomal recessive CARD9 deficiency; central nervous system; invasive fungal infection; osteomyelitis; parental unidisomy