title: Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics.
abstract: BACKGROUND
  Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by early onset of recurrent and severe infections. The molecular defects causing CGD are heterogeneous and lead to absence, low expression, or malfunctioning of one of the phagocyte NADPH oxidase components. The aim of this study was to analyze the clinical features and to investigate the molecular genetic defects of Latin American patients with CGD.
  
  
  METHODS
  The study included 14 patients. The diagnosis was based on a history of recurrent severe infections, impaired respiratory burst, and the demonstration of an underlying mutation by single strand conformation polymorphism (SSCP) or RT-PCR analysis, followed by genomic DNA or cDNA sequencing.
  
  
  RESULTS
  Seven unrelated patients were found to have the X-linked form of CGD (X-CGD). Heterogeneous mutations affected the CYBB gene: two insertions, one substitution, and four splice site defects; two of them are novel. Seven patients presented with one of the autosomal recessive forms of CGD (A47-CGD); all had the most common mutation, a DeltaGT deletion in exon 2 of the NCF1 gene. Pneumonia was the most frequent clinical feature, followed by pyoderma, sinusitis, otitis, and liver abscess. Patients with X-CGD were more likely to have initial infections before age 2 years and to have inflammatory obstructive granulomas later. None of the patients had severe adverse reactions to BCG immunization.
  
  
  CONCLUSIONS
  X-CGD patients from Latin America showed a high degree of molecular heterogeneity, including two novel mutations. Their clinical characteristics included early onset of infections and eventual obstructive granulomas. A47-CGD represented 50% of the reported cases, a higher prevalence than reported in other series.
authors.affiliation: Center for Investigation in Pediatrics and Department of Pediatrics, State University of Campinas Medical School, Campinas, Sao Paulo, Brazil.
authors.forename: Piedad
authors.initials: P
authors.lastname: Agudelo-Flórez
authors.forename: Carolina Cardoso
authors.initials: CC
authors.lastname: Prando-Andrade
authors.forename: Juan Alvaro
authors.initials: JA
authors.lastname: López
authors.forename: Beatriz Tavares
authors.initials: BT
authors.lastname: Costa-Carvalho
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Quezada
authors.forename: Francisco Jose
authors.initials: FJ
authors.lastname: Espinosa
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: de Souza Paiva
authors.forename: Persio
authors.initials: P
authors.lastname: Roxo
authors.forename: Anete
authors.initials: A
authors.lastname: Grumach
authors.forename: Cristina Abe
authors.initials: CA
authors.lastname: Jacob
authors.forename: Magda Maria Salles
authors.initials: MM
authors.lastname: Carneiro-Sampaio
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
authors.forename: Antonio
authors.initials: A
authors.lastname: Condino-Neto
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000235:genetics*; D006801:Humans; D007843:Latin America; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D016254:Mutagenesis, Insertional; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D022821:RNA Splice Sites / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion
chemical_list: D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D022821:RNA Splice Sites; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1