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

• DOI: 10.1007/s10875-018-0549-0
• Publication Date: 2018-09-28T00:26:48Z
• Authors: Carlos A. Arango-...; Marcela Moncada-V...; Claudia Patricia ...; Indira Berrío; Cristian Mogollón; Andrea Restrepo; Mónica Trujillo; Sara Daniela Osorio; Lorena Castro; Lina Vanessa Gómez; Ana María Muñoz; Verónica Molina; Delsy Yurledy del...; Ana Cristina Ruiz; Carlos Garcés; Juan Fernando Alzate; Felipe Cabarcas; Julio Cesar Orrego; Jean-Laurent Casa...; Jacinta Bustamante; Anne Puel; Andrés Augusto Arias; José Luis Franco
• Keywords: 0301 basic medicine; Heterozygote; DNA Mutational Analysis; Age Factors; Computational Biology; Colombia; Immunohistochemistry; Magnetic Resonance Imaging; Immunophenotyping; Pedigree; 3. Good health; CARD Signaling Adaptor Proteins; Phaeohyphomycosis; 03 medical and health sciences; Ascomycota; Child, Preschool; Mutation; Humans; Female; Genetic Predisposition to Disease; Age of Onset; Biomarkers; Invasive Fungal Infections

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.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.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.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.