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

Autor: Arango-Franco CA; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.; Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Moncada-Vélez M; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Beltrán CP; Departamento de Pediatría, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Berrío I; Medical and Experimental Mycology Group, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia.; Hospital General de Medellín 'Luz Castro de Gutiérrez' ESE, Medellín, Colombia., Mogollón C; Infectología, Hospital Universitario Fernando Troconnis, Santa Marta, Colombia., Restrepo A; Hospital Pablo Tobón Uribe, Medellín, Colombia., Trujillo M; Hospital Pablo Tobón Uribe, Medellín, Colombia., Osorio SD; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.; Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Castro L; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.; Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Gómez LV; Hospital Pablo Tobón Uribe, Medellín, Colombia.; Servicio de Dermatología, Universidad Pontificia Bolivariana, Medellín, Colombia., Muñoz AM; Servicio de Dermatología, Universidad Pontificia Bolivariana, Medellín, Colombia., Molina V; Hospital Pablo Tobón Uribe, Medellín, Colombia.; Servicio de Dermatología, Universidad Pontificia Bolivariana, Medellín, Colombia., Del Río Cobaleda DY; Hospital Pablo Tobón Uribe, Medellín, Colombia., Ruiz AC; Hospital Pablo Tobón Uribe, Medellín, Colombia., Garcés C; Departamento de Pediatría, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.; Hospital Pablo Tobón Uribe, Medellín, Colombia., Alzate JF; Centro Nacional de Secuenciación Genómica CNSG, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia., Cabarcas F; Centro Nacional de Secuenciación Genómica CNSG, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.; Grupo SISTEMIC, Facultad de Ingeniería, Universidad de Antioquia UdeA , Calle 70 No 52-21, Medellín, Colombia., Orrego JC; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia., Casanova JL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM-U1163, Paris, EU, France.; Imagine Institute, Paris Descartes University, Paris, EU, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.; Howard Hughes Medical Institute, New York, NY, USA., Bustamante J; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM-U1163, Paris, EU, France.; Imagine Institute, Paris Descartes University, Paris, EU, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.; Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, Paris, EU, France., Puel A; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM-U1163, Paris, EU, France.; Imagine Institute, Paris Descartes University, Paris, EU, France.; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA., Arias AA; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. aaugusto.arias@udea.edu.co.; Escuela de Microbiología, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. aaugusto.arias@udea.edu.co., Franco JL; Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2018 Oct; Vol. 38 (7), pp. 794-803. Date of Electronic Publication: 2018 Sep 28.
DOI: 10.1007/s10875-018-0549-0
Abstrakt: 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.
Databáze: MEDLINE
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