title: A homozygous CARD9 mutation in a Brazilian patient with deep dermatophytosis.
abstract: Deep dermatophytosis has been described in HIV and immunosuppressed patients. Recently, CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in individuals with deep dermatophytosis previously classified as "immunocompetent". We report a 24-year-old Brazilian male patient with deep dermatophytosis born to an apparently non-consanguineous family. The symptoms started with oral candidiasis when he was 3 years old, persistent although treated. At 11 years old, well delimited, desquamative and pruriginous skin lesions appeared in the mandibular area; ketoconazole and itraconazole were introduced and maintained for 5 years. At 12 years of age, the lesions, which initially affected the face, started to spread to thoracic and back of the body (15 cm of diameter) and became ulcerative, secretive and painful. Terbinafine was introduced without any improvement. Trichophyton mentagrophytes was isolated from the skin lesions. A novel homozygous mutation in CARD9 (R101L) was identified in the patient, resulting in impaired neutrophil fungal killing. Both parents, one brother (with persistent superficial but not deep dermatophytosis) and one sister were heterozygous for this mutation, while another brother was found to be homozygous for the CARD9 wild-type allele. This is the first report of CARD9 deficiency in Latin America.
authors.affiliation: Outpatient Group of Recurrent Infections, Faculty of Medicine ABC, Santo Andre, SP, Brazil, asgrumach@gmail.com.
authors.forename: Anete S
authors.initials: AS
authors.lastname: Grumach
authors.forename: Flavio
authors.initials: F
authors.lastname: de Queiroz-Telles
authors.forename: Mélanie
authors.initials: M
authors.lastname: Migaud
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.forename: Nelson Rosario
authors.initials: NR
authors.lastname: Filho
authors.forename: Sandra M U
authors.initials: SM
authors.lastname: Palma
authors.forename: Rosemeire Navickas
authors.initials: RN
authors.lastname: Constantino-Silva
authors.forename: Jean Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
mesh_terms: D000328:Adult; D001938:Brazil; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics* / Q000302:isolation & purification; D002180:Candidiasis, Oral / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology*; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics; D012867:Skin / Q000382:microbiology / Q000473:pathology*; D014005:Tinea / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human