Early-Onset Invasive Infection Due to Corynespora cassiicola Associated with Compound Heterozygous CARD9 Mutations in a Colombian Patient

Purpose CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida , but also by dermatophytes, Aspergillus , and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused...

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Published in:	Journal of clinical immunology Vol. 38; no. 7; pp. 794 - 803
Main Authors:	Arango-Franco, Carlos A., Moncada-Vélez, Marcela, Beltrán, Claudia Patricia, Berrío, Indira, Mogollón, Cristian, Restrepo, Andrea, Trujillo, Mónica, Osorio, Sara Daniela, Castro, Lorena, Gómez, Lina Vanessa, Muñoz, Ana María, Molina, Verónica, del Río Cobaleda, Delsy Yurledy, Ruiz, Ana Cristina, Garcés, Carlos, Alzate, Juan Fernando, Cabarcas, Felipe, Orrego, Julio Cesar, Casanova, Jean-Laurent, Bustamante, Jacinta, Puel, Anne, Arias, Andrés Augusto, Franco, José Luis
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-10-2018 Springer Nature B.V
Subjects:	Age Biomedical and Life Sciences Biomedicine Clonal deletion Fungal infections Fungi Gene deletion Immunology Infectious Diseases Internal Medicine Leukocytes (mononuclear) Medical Microbiology Medical records Mutation Nonsense mutation Original Article Peripheral blood mononuclear cells Phaeohyphomycosis Protein expression Stop codon Western blotting primary immunodeficiency compound heterozygous mutations invasive fungal disease Phaeohyphomycosis inborn errors of immunity CARD9 Corynespora cassiicola
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Summary:	Purpose CARD9 deficiency is an inborn error of immunity that predisposes otherwise healthy humans to mucocutaneous and invasive fungal infections, mostly caused by Candida , but also by dermatophytes, Aspergillus , and other fungi. Phaeohyphomycosis are an emerging group of fungal infections caused by dematiaceous fungi (phaeohyphomycetes) and are being increasingly identified in patients with CARD9 deficiency. The Corynespora genus belongs to phaeohyphomycetes and only one adult patient with CARD9 deficiency has been reported to suffer from invasive disease caused by C . cassiicola . We identified a Colombian child with an early-onset, deep, and destructive mucocutaneous infection due to C . cassiicola and we searched for mutations in CARD9 . Methods We reviewed the medical records and immunological findings in the patient. Microbiologic tests and biopsies were performed. Whole-exome sequencing (WES) was made and Sanger sequencing was used to confirm the CARD9 mutations in the patient and her family. Finally, CARD9 protein expression was evaluated in peripheral blood mononuclear cells (PBMC) by western blotting. Results The patient was affected by a large, indurated, foul-smelling, and verrucous ulcerated lesion on the left side of the face with extensive necrosis and crusting, due to a C . cassiicola infectious disease. WES led to the identification of compound heterozygous mutations in the patient consisting of the previously reported p.Q289* nonsense (c.865C > T, exon 6) mutation, and a novel deletion (c.23_29del; p.Asp8Alafs10*) leading to a frameshift and a premature stop codon in exon 2. CARD9 protein expression was absent in peripheral blood mononuclear cells from the patient. Conclusion We describe here compound heterozygous loss-of-expression mutations in CARD9 leading to severe deep and destructive mucocutaneous phaeohyphomycosis due to C . cassiicola in a Colombian child.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0271-9142 1573-2592
DOI:	10.1007/s10875-018-0549-0