ABSTRACT
BACKGROUND: The X-linked form of chronic granulomatous disease (CGD) is a primary immunodeficiency that affects phagocytes of the innate immune system and is characterized by an increased susceptibility to severe bacterial and fungal infections. It is caused by mutations in the CYBB gene, which encodes the 91-kD subunit of phagocyte NADPH oxidase. AIM: To identify the mutation in the CYBB gene in two unrelated patients from Chile with the diagnosis of X-linked CGD and their families. PATIENTS AND METHODS: The molecular genetic defects of two unrelated patients from Chile with X-linked CGD caused by defects in the CYBB gene were investigated. The underlying mutation was investigated by single strand conformation polymorphism (SSCP) analysis of PCR-amplified genomic DNA and by sequencing of the affected gene region. RESULTS: We found an insertion c.1267_1268insA in exon 10 leading to a frameshift mutation. This mutation is a novel report. We also identified a splice site mutation in the other patient, that presented a c.1326 +1 G>A substitution in intron 10. The mutation was also detectable in his heterozygous mother. CONCLUSIONS: This is the first report of the clinical and molecular characterization of Chilean patients with mutations in CYBB gene.
Subject(s)
Frameshift Mutation/genetics , Granulomatous Disease, Chronic/genetics , Membrane Glycoproteins/genetics , Mutagenesis, Insertional/genetics , NADPH Oxidases/genetics , Case-Control Studies , Child , Child, Preschool , Chile , Granulomatous Disease, Chronic/diagnosis , Humans , Male , NADPH Oxidase 2 , RNA Splice Sites , Sequence Analysis, DNAABSTRACT
BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. More than 900 mutations have been detected in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. The most common worldwide, is a deletion of phenylalanine 508 (delta F508). AIM: To analyze the presence of mutations delta F508, G542X, N1303K, G551D, R553X and S549N in patients from the 5th Region of Chile, with a clinical diagnosis of CF. PATIENTS AND METHODS: We studied 17 non-related patients, presenting frequent respiratory tract infections, malabsorption and positive sweat tests, or meconial ileum. Serum immunoglobulins (IgG, IgA, IgM), and total, CD3+ and B-lymphocytes, were determined to discard the presence of an immune deficiency. The molecular study of the gene was performed by Polymerase Chain Reaction amplification and restriction analysis. RESULTS: Immunological parameters were normal in all patients. The delta F508 mutation was detected in 11 chromosomes and the mutation G542X in 3 chromosomes. CONCLUSIONS: The mutation G542X was the second most frequent mutation found in this sample of Chilean CF patients. Since this mutation has a high frequency in Spanish CF patients, we suggest that this mutation might have had its origin in Spain.
