[Report of a new mutation in CYBB gene in two patients with X linked chronic granulomatous disease]. / Identificación de mutaciones en el gen CYBB que llevan al fenotipo de la enfermedad granulomatosa crónica ligada al cromosoma X: reporte de una nueva mutación.

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.

[Hyper-IgM syndrome in members of two unrelated Chilean families: molecular and mutation analysis]. / Síndrome de hiper-IgM en miembros de 2 familias Chilenas no relacionadas: análisis genético- molecular.

BACKGROUND: Hyper-IgM syndronie (HIGM) is a rare primary immunodeficiency used to describe a heterogeneous group of disorders characterized by recurrey bacterial infrctions, normal or elevated serum IgM levels and low or absent serum IgG, IgA and IgE. AIM: To make definitive diagnosis, detect mutations in carriers and perform genetic counseling in patients with HIGM. PATIENTS AND METHODS: We studied the expression of CD40L, CD40 and made a mutation analysis of the CD40L gene in 3 males of 2 unrelated Chilean families diagnosed as a possible syndrome of hyper-IgM and 3 relatives. RESULTS: We identified a deletion frameshift in the exon 2 (delA225) of the extracellular domain of GD40L gene in one patient and verified the carrier stains of his mother and sister. The other patients showed a low expression of GD40L in activated T cells (65.3% ammd 65.5%) and a normal expressiomi of CD40. No alterations were found in the single strand conformation polymorphism analysis of the CD40L. CONCLUSIONS: These result allowed us to make a definite diagnosis of HIGM1 of a patient, detect female carriers and suggest a HIGM of recessive inheritance with normal CD40 expression in the patients of the second family.