Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection
Fanny Lanternier
(1, 2, 3)
,
Elisa Barbati
(3)
,
Ulrich Meinzer
(4, 5)
,
Luyan Liu
(3)
,
Vincent Pedergnana
(3)
,
Mélanie Migaud
(3)
,
Sébastien Héritier
(1, 6)
,
Maryline Chomton
(1, 6)
,
Marie-Louise Fremond
(1, 6)
,
Emmanuel Gonzales
(1, 7)
,
Caroline Galeotti
(1, 8)
,
Serge Romana
(1)
,
Emmanuel Jacquemin
(1, 9)
,
Adela Angoulvant
(1)
,
Valeska Bidault
(1)
,
Danielle Canioni
(1)
,
Julie Lachenaud
(10)
,
Davood Mansouri
(11)
,
Seyed Alireza Mahdaviani
(12)
,
Parvaneh Adimi
(13)
,
Nahal Mansouri
(11)
,
Mahin Jamshidi
(14)
,
Marie-Elisabeth Bougnoux
(15, 1, 16)
,
Laurent Abel
(17, 3)
,
Olivier Lortholary
(16, 2, 18)
,
Stephane Blanche
(1, 16)
,
Jean-Laurent Casanova
(1, 17, 3)
,
Capucine Picard
(1, 3)
,
Anne Puel
(3)
1
AP-HP -
Assistance publique - Hôpitaux de Paris (AP-HP)
2 Centre d'infectiologie Necker-Pasteur [CHU Necker]
3 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
4 UPD7 - Université Paris Diderot - Paris 7
5 AP-HP Hôpital universitaire Robert-Debré [Paris]
6 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
7 DHU Hepatinov
8 CeRéMAIA - Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre]
9 Signalisation calcique et interactions cellulaires dans le foie
10 Centre Hospitalier René Dubos [Pontoise]
11 Masih Daneshvari Hospital
12 Shahid Beheshti University
13 Islamic Azad University
14 Department of Infectious Disease
15 BPF - Biologie et Pathogénicité fongiques
16 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
17 Rockefeller University [New York]
18 CNRMA - Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire
2 Centre d'infectiologie Necker-Pasteur [CHU Necker]
3 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
4 UPD7 - Université Paris Diderot - Paris 7
5 AP-HP Hôpital universitaire Robert-Debré [Paris]
6 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
7 DHU Hepatinov
8 CeRéMAIA - Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre]
9 Signalisation calcique et interactions cellulaires dans le foie
10 Centre Hospitalier René Dubos [Pontoise]
11 Masih Daneshvari Hospital
12 Shahid Beheshti University
13 Islamic Azad University
14 Department of Infectious Disease
15 BPF - Biologie et Pathogénicité fongiques
16 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
17 Rockefeller University [New York]
18 CNRMA - Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire
Ulrich Meinzer
- Fonction : Auteur
- PersonId : 784468
- ORCID : 0000-0001-8539-6507
- IdRef : 268894833
Vincent Pedergnana
- Fonction : Auteur
- PersonId : 174866
- IdHAL : vincent-pedergnana
- ORCID : 0000-0002-7852-5339
- IdRef : 175475547
Mélanie Migaud
- Fonction : Auteur
- PersonId : 769678
- ORCID : 0000-0003-3062-1214
Emmanuel Gonzales
- Fonction : Auteur
- PersonId : 800862
- ORCID : 0000-0002-1546-3193
- IdRef : 111751063
Emmanuel Jacquemin
- Fonction : Auteur
- PersonId : 759737
- ORCID : 0000-0002-7536-6272
- IdRef : 111751144
Adela Angoulvant
- Fonction : Auteur
- PersonId : 769323
- ORCID : 0000-0001-7035-8946
Davood Mansouri
- Fonction : Auteur
- PersonId : 762966
- ORCID : 0000-0002-1927-7072
Seyed Alireza Mahdaviani
- Fonction : Auteur
- PersonId : 779164
- ORCID : 0000-0001-6224-4797
Marie-Elisabeth Bougnoux
- Fonction : Auteur
- PersonId : 758331
- ORCID : 0000-0003-4721-2740
Laurent Abel
- Fonction : Auteur
- PersonId : 756191
- ORCID : 0000-0001-7016-6493
- IdRef : 07779432X
Jean-Laurent Casanova
- Fonction : Auteur
- PersonId : 756193
- ORCID : 0000-0002-7782-4169
- IdRef : 073388726
Capucine Picard
- Fonction : Auteur
- PersonId : 758297
- ORCID : 0000-0001-8788-5056
- IdRef : 091572363
Anne Puel
- Fonction : Auteur
- PersonId : 1039617
Résumé
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.