Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics.
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.
Agudelo-Flórez
Piedad
P
Center for Investigation in Pediatrics and Department of Pediatrics, State University of Campinas Medical School, Campinas, Sao Paulo, Brazil.
Prando-Andrade
Carolina Cardoso
CC
López
Juan Alvaro
JA
Costa-Carvalho
Beatriz Tavares
BT
Quezada
Arnoldo
A
Espinosa
Francisco Jose
FJ
de Souza Paiva
Maria Aparecida
MA
Roxo
Persio
P
Grumach
Anete
A
Jacob
Cristina Abe
CA
Carneiro-Sampaio
Magda Maria Salles
MM
Newburger
Peter E
PE
Condino-Neto
Antonio
A
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
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