Chronic granulomatous disease in Latin American patients: Clinical spectrum and molecular genetics

• Published in: Pediatric Blood & Cancer 2006-02, Vol.46 (2), p.243-252
• Main Authors: Agudelo-Flórez, Piedad, Prando-Andrade, Carolina Cardoso, López, Juan Alvaro, Costa-Carvalho, Beatriz Tavares, Quezada, Arnoldo, Espinosa, Francisco Jose, de Souza Paiva, Maria Aparecida, Roxo Jr, Persio, Grumach, Anete, Jacob, Cristina Abe, Carneiro-Sampaio, Magda Maria Salles, Newburger, Peter E., Condino-Neto, Antonio
• Format: Article
• Language: English
• Subjects: BCG; Biological and medical sciences; chronic granulomatous disease; DNA Mutational Analysis - methods; Exons - genetics; Female; General aspects; Genes, Recessive - genetics; Granulomatous Disease, Chronic - complications; Granulomatous Disease, Chronic - genetics; Humans; Latin America; Male; Medical sciences; Membrane Glycoproteins - genetics; Mutagenesis, Insertional; mutations; NADPH Oxidase 2; NADPH Oxidases - genetics; neutrophils; phagocytes; Phosphoproteins - genetics; Polymorphism, Single-Stranded Conformational; primary immunodeficiencies; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA Splice Sites - genetics; Sequence Deletion; Tumors
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.20455

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. Procedures 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 ΔGT 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. © 2005 Wiley‐Liss, Inc.