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A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections
Open accessAbstract
BACKGROUND: Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. METHODS: We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. RESULTS: We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin-17). Functional studies based on genetic reconstitution of myeloid cells from Card9(-/-) mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. CONCLUSIONS: An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9.
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“Defects in the CARD9 pathway have been found predisposing to chronic mucocutaneous candidiasis [28] and disseminated aspergillosis [29]”
From Race and ethnicity: Risk factors for fungal infections? (2023) · cites this paper as [28]
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Citations
Cites
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606
Strategies for multilocus linkage analysis in humans.
Lathrop, M. G., Lalouel, J.-M., Julier, C., & Ott, J. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.11.3443 · Cited by 2,560
Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2
Gantner, B. N., Simmons, R. M., Canavera, S. J., Akira, S., & Underhill, D. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021787 · Cited by 1,682
Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060468 · Cited by 1,512
Positional cloning of the APECED gene
Nagamine, K., Peterson, P., Scott, H. S., Kudoh, J., Minoshima, S., Heino, M., Krohn, K. J. E., Lalioti, M. D., Mullis, P. E., Antonarakis, S. E., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-393 · Cited by 1,439
Faster sequential genetic linkage computations.
Cottingham, R. W., Idury, R. M., & Schäffer, A. A. (1993) · Europe PMC (PubMed Central) · Cited by 1,364
Self-citationSTAT3 Mutations in the Hyper-IgE Syndrome
Holland, S. M., DeLeo, F. R., Elloumi, H. Z., Hsu, A. P., Uzel, G., Brodsky, N. N., Freeman, A. F., Demidowich, A. P., Davis, J., Turner, M. L. C., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa073687 · Cited by 1,233
Self-citationAaltonen, J., Björses, P., Perheentupa, J., Horelli‐Kuitunen, N., Palotie, A. V., Peltonen, L., Lee, Y. S., Francis, F., Henning, S., Thiel, C. S., et al. (1997) · Nature Genetics · doi:10.1038/ng1297-399 · Cited by 1,214
LeibundGut-Landmann, S., Groß, O., Robinson, M. J., Osorio, F., Slack, E. C., Tsoni, S. V., Schweighoffer, E., Tybulewicz, V., Brown, G. D., Ruland, J., et al. (2007) · Nature Immunology · doi:10.1038/ni1460 · Cited by 1,191
Self-citationDectin-1 is required for β-glucan recognition and control of fungal infection
Taylor, P. R., Tsoni, S. V., Willment, J. A., Dennehy, K. M., Rosas, M., Findon, H., Haynes, K., Steele, C. H., Botto, M., Gordon, S., et al. (2006) · Nature Immunology · doi:10.1038/ni1408 · Cited by 1,185
Dectin-1: a signalling non-TLR pattern-recognition receptor
Brown, G. D. (2006) · Nature Reviews Immunology · doi:10.1038/nri1745 · Cited by 1,158
Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome
Milner, J. D., Brenchley, J. M., Laurence, A., Freeman, A. F., Hill, B. J., Elias, K. M., Kanno, Y., Spalding, C., Elloumi, H. Z., Paulson, M. L., et al. (2008) · Nature · doi:10.1038/nature06764 · Cited by 1,157
Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome
Minegishi, Y., Saitō, M., Tsuchiya, S., Tsuge, I., Takada, H., Hara, T., Kawamura, N., Ariga, T., Pašić, S., Stojković, O., et al. (2007) · Nature · doi:10.1038/nature06096 · Cited by 1,075
Ahonen, P., Myllärniemi, S., Sipilä, I., & Perheentupa, J. (1990) · New England Journal of Medicine · doi:10.1056/nejm199006283222601 · Cited by 1,068
Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081463 · Cited by 1,024
Epidemiology of Candida species infections in critically ill non-immunosuppressed patients
Eggimann, P., Garbino, J., & Pittet, D. (2003) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(03)00801-6 · Cited by 900
Rogers, N. C., Slack, E. M. C., Edwards, A. D., Nolte, M. A., Schulz, O., Schweighoffer, E., Williams, D. L., Gordon, S., Tybulewicz, V. L. J., Brown, G. D., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.03.004 · Cited by 897
Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity
Groß, O., Gewies, A., Finger, K., Schäfer, M., Sparwasser, T. D., Peschel, C., Förster, I., & Ruland, J. (2006) · Nature · doi:10.1038/nature04926 · Cited by 871
Self-citationRequirement of Interleukin‐17A for Systemic Anti– Candida albicans Host Defense in Mice
Huang, W., Na, L., Fidel, P. L., & Schwarzenberger, P. (2004) · The Journal of Infectious Diseases · doi:10.1086/422329 · Cited by 859
Hyper-IgE Syndrome with Recurrent Infections — An Autosomal Dominant Multisystem Disorder
Grimbacher, B., Holland, S. M., Gallin, J. I., Greenberg, F., Hill, S. C., Malech, H. L., Miller, J., O’Connell, A. C., & Puck, J. M. (1999) · New England Journal of Medicine · doi:10.1056/nejm199903043400904 · Cited by 801
Self-citationMincle is an ITAM-coupled activating receptor that senses damaged cells
Yamasaki, S., Ishikawa, E., Sakuma, M., Hara, H., Ogata, K., & Saito, T. (2008) · Nature Immunology · doi:10.1038/ni.1651 · Cited by 740
Avoiding Recomputation in Linkage Analysis
Schäffer, A. A., Gupta, S. K., Shriram, K. M. P., & Cottingham, R. W. (1994) · Human Heredity · doi:10.1159/000154222 · Cited by 668
Self-citationDeficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3
Ma, C. S., Chew, G. Y. J., Simpson, N., Priyadarshi, A., Wong, M., Grimbacher, B., Fulcher, D. A., Tangye, S. G., & Cook, M. C. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080218 · Cited by 652
Self-citationDillon, S. M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27203 · Cited by 550
Sato, K., Yang, X.-L., Yudate, T., Chung, J., Wu, J., Luby‐Phelps, K., Kimberly, R. P., Underhill, D. M., Cruz, P. D., & Ariizumi, K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606542200 · Cited by 470
Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages
Herre, J. (2004) · Blood · doi:10.1182/blood-2004-03-1140 · Cited by 464
The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens
Hsu, Y.-M. S., Zhang, Y., You, Y., Wang, D., Li, H., Duramad, O., Qin, F. X.-F., Dong, C., & Lin, X. (2006) · Nature Immunology · doi:10.1038/ni1426 · Cited by 420
Goodridge, H. S., Simmons, R. M., & Underhill, D. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.3107 · Cited by 365
A genotype calling algorithm for affymetrix SNP arrays
Rabbee, N., & Speed, T. P. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti741 · Cited by 363
Unravelling the Complexity of T Cell Abnormalities in Common Variable Immunodeficiency
Giovannetti, A., Pierdominici, M., Mazzetta, F., Marziali, M., Renzi, C., Mileo, A. M., Felice, M. D., Mora, B., Esposito, A., Carello, R., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.6.3932 · Cited by 277
C-type lectin receptors in antifungal immunity
Willment, J. A., & Brown, G. D. (2007) · Trends in Microbiology · doi:10.1016/j.tim.2007.10.012 · Cited by 277
Exact genetic linkage computations for general pedigrees
Fishelson, M., & Geiger, D. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.suppl_1.s189 · Cited by 255
Eyerich, K., Foerster, S., Rombold, S., Seidl, H., Behrendt, H., Hofmann, H., Ring, J., & Traidl‐Hoffmann, C. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.139 · Cited by 251
Chronic mucocutaneous candidiasis
Kirkpatrick, C. H. (2001) · The Pediatric Infectious Disease Journal · doi:10.1097/00006454-200102000-00017 · Cited by 236
Bertin, J., Guo, Y., Wang, L., Srinivasula, S. M., Jacobson, M. D., Poyet, J., Merriam, S., Du, M., Dyer, M. J. S., Robison, K. E., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000726200 · Cited by 232
Underhill, D. M., & Goodridge, H. S. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.12.004 · Cited by 193
Scoy, R. E. V., Hill, H. R., RITTS, R. E., & QUIE, P. G. (1975) · Annals of Internal Medicine · doi:10.7326/0003-4819-82-6-766 · Cited by 171
Romagnani, S. (2008) · Arthritis Research & Therapy · doi:10.1186/ar2392 · Cited by 163
IMMUNOLOGICAL OBSERVATIONS IN CHRONIC MUCOCUTANEOUS CANDIDIASIS
Canales, L., Middlemas, R., Louro, J., & South, M. A. (1969) · The Lancet · doi:10.1016/s0140-6736(69)90264-5 · Cited by 118
New perspectives on the immunology of chronic mucocutaneous candidiasis
Lilić, D. (2002) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200204000-00007 · Cited by 116
Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans
Bugarc̀ić, A., Hitchens, K., Beckhouse, A. G., Wells, C. A., Ashman, R. B., & Blanchard, H. (2008) · Glycobiology · doi:10.1093/glycob/cwn046 · Cited by 116
CHRONIC TETANY AND CHRONIC MYCELIAL STOMATITIS IN A CHILD AGED FOUR AND ONE-HALF YEARS
THORPE, E. S. (1929) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1929.01930080104011 · Cited by 112
Familial chronic muco-cutaneous candidiasis.
Wells, R. S., Higgs, J. M., Macdonald, A., Valdimarsson, H., & Holt, P. J. L. (1972) · Journal of Medical Genetics · doi:10.1136/jmg.9.3.302 · Cited by 96
Silberstein, M., Tzemach, A., Dovgolevsky, N., Fishelson, M., Schuster, A., & Geiger, D. (2006) · The American Journal of Human Genetics · doi:10.1086/504158 · Cited by 88
Drouhet, E., & Dupont, B. (1980) · Clinical Infectious Diseases · doi:10.1093/clinids/2.4.606 · Cited by 82
Giovannetti, A., Mazzetta, F., Caprini, E., Aiuti, A., Marziali, M., Pierdominici, M., Cossarizza, A., Chessa, L., Scala, E., Quinti, I., et al. (2002) · Blood · doi:10.1182/blood-2002-03-0976 · Cited by 82
Chronic mucocutaneous candidiasis
SAMS, W. M., Jorizzo, J. L., D, R. S. M., Jegasothy, B. V., Ward, F. E., WEINER, M. H., Wilson, J. G., Yount, W. J., & Dillard, S. B. (1979) · The American Journal of Medicine · doi:10.1016/0002-9343(79)90635-1 · Cited by 55
Colonna, M. (2007) · Nature Immunology · doi:10.1038/ni0607-554 · Cited by 51
Miething, C., Grundler, R., Fend, F., Hoepfl, J., Mugler, C., von Schilling, C., Morris, S. W., Peschel, C., & Duyster, J. (2003) · Oncogene · doi:10.1038/sj.onc.1206575 · Cited by 50
Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q
Finck, A., van der Meer, J. W. M., Schäffer, A. A., Pfannstiel, J., Fieschi, C., Plebani, A., WEBSTER, A. D. B., Hammarström, L. L. G., & Grimbacher, B. (2006) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201634 · Cited by 49
Self-citationAtkinson, T. P., Schäffer, A. A., Grimbacher, B., Schroeder, H. W., Woellner, C., Zerbe, C. S., & Puck, J. M. (2001) · The American Journal of Human Genetics · doi:10.1086/323611 · Cited by 44
Self-citationTreatment of Two Cases of Cryptococcai Meningitis with Fluconazole
Wout, J. W. V. ’., de Graeff-Meeder, E. R., Paul, L., Kuis, W., & van Furth, R. (1988) · Scandinavian Journal of Infectious Diseases · doi:10.3109/00365548809032437 · Cited by 32
Invasive Fungal Infections in Patients With Chronic Mucocutaneous Candidiasis
Kauffman, C. A. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.1981.00340080112024 · Cited by 29
Fungal intracranial aneurysm in a child with familial chronic mucocutaneous candidiasis
Loeys, B., Coster, R. N. V., Defreyne, L., & Leroy, J. G. (1999) · European Journal of Pediatrics · doi:10.1007/s004310051169 · Cited by 25
Caspase recruitment domain-containing sensors and adaptors in intestinal innate immunity
Hruz, P. L., & Eckmann, L. (2008) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3282f50fdf · Cited by 25
Mucocutaneous Candidiasis in a Mother and Son
Kroll, J. J. (1973) · Archives of Dermatology · doi:10.1001/archderm.1973.01620230055020 · Cited by 12
A gene for familial isolated chronic nail candidiasis maps to chromosome 11p12–q12.1
Mangino, M., Salpietro, D. C., Zuccarello, D., Gangemi, S., Rigoli, L. C., Merlino, M. V., Briuglia, S., Bisignano, G., Mingarelli, R., & Dallapiccola, B. (2003) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200985 · Cited by 10
The hyper-IgE syndrome is not caused by a microdeletion syndrome
Pfeifer, D., Woellner, C., Petersen, A. C., Pietrogrande, M. C., Franco, J. L., Yeganeh, M., Ehl, S. R., Matamoros, N., Sprecher, E., Puck, J. M., et al. (2007) · Immunogenetics · doi:10.1007/s00251-007-0257-z · Cited by 7
Self-citationInvasive fungal infections in patients with chronic mucocutaneous candidiasis
Kauffman, C. A. (1981) · Archives of Internal Medicine · doi:10.1001/archinte.141.8.1076 · Cited by 5
Mucocutaneous candidiasis in a mother and son
Kroll, J. J. (1973) · Archives of Dermatology · doi:10.1001/archderm.108.2.259 · Cited by 5
Research works printed but not linked: 2
- Thorpe ES, 1929, Am J Dis Child, 38, 328
- Cottingham RW, 1993, Am J Hum Genet, 53, 252
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Metadata
- Authors
- Glocker, E.-O., Hennigs, A., Nabavi, M., Schäffer, A. A., Woellner, C., Salzer, U., Pfeifer, D., Veelken, H., Warnatz, K., Tahami, F., Jamal, S., Manguiat, A., Rezaei, N., Amirzargar, A. A., Plebani, A., Hannesschläger, N., Gross, O., Ruland, J., & Grimbacher, B.
- Affiliations
- University of London (GB)
- Semnan University of Medical Sciences (IR)
- National Institutes of Health (US)
- University Medical Center Freiburg (DE)
- Children's Medical Center (US)
- Tehran University of Medical Sciences (IR)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- TUM Klinikum (DE)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2009-10-29
- Volume
- 361
- Issue
- 18
- Pages
- 1727-1735
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2793117
- OpenAlex
- W2164500783
- Cited by
- 800
- References
- 58
- Citations by year
- 2026: 24 · 2025: 23 · 2024: 28 · 2023: 37 · 2022: 41 · 2021: 43 · 2020: 48 · 2019: 45 · 2018: 51 · 2017: 53 · 2016: 50 · 2015: 63 · 2014: 59 · 2013: 44 · 2012: 56
- FWCI
- 27.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Funders
- National Institutes of Health (Z99 LM999999)
- U.S. National Library of Medicine (ZIALM000097)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- CARD9, chronic mucocutaneous candidiasis, fungal infection susceptibility, primary immunodeficiency, homozygous mutation, autosomal recessive inheritance, consanguineous family, Th17 cells, Dectin-1
- MeSH terms
- Adolescent, Animals, Candida, Candidiasis, Candidiasis, Chronic Mucocutaneous, Consanguinity, DNA Mutational Analysis, Female, Genes, Recessive, Homozygote, Humans, Lod Score, Male, Middle Aged, Pedigree, RNA, Messenger, T-Lymphocytes, Signal Transduction, Meningitis, Fungal, Mice, Knockout, Codon, Nonsense, Genetic Predisposition to Disease, Mice, CARD Signaling Adaptor Proteins, Young Adult
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