Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics
prando-Andrade, Carolina Cardoso
Lopez, Juan Alvaro
Costa-Carvalho, Beatriz Tavares
Espinosa, Francisco Jose
de Souza Paiva, Maria Aparecida
Roxo, Persio Jr.
Jacob, Cristina Abe
Carneiro-Sampaio, Magda Maria Salles
Newburger, Peter E.
UMass Chan AffiliationsDepartment of Pediatrics
Document TypeJournal Article
KeywordsDNA Mutational Analysis
Granulomatous Disease, Chronic
*Polymorphism, Single-Stranded Conformational
RNA Splice Sites
Reverse Transcriptase Polymerase Chain Reaction
MetadataShow full item record
AbstractBACKGROUND: 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 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.
SourcePediatr Blood Cancer. 2006 Feb;46(2):243-52. doi: 10.1002/pbc.20455
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43407
Related ResourcesLink to article in PubMed