RT Journal Article
T1 A Point Mutation in a Domain of Gamma Interferon Receptor 1 Provokes Severe Immunodeficiency
A1 Allende Martínez, Luis Miguel
A1 López Goyanes, Alberto
A1 Paz Artal, Estela Natividad
A1 Corell, Alfredo
A1 García Pérez, Miguel Ángel
A1 Varela Peña, Pilar
A1 Scarpellini, Atilio
A1 Negreira, Sagrario
A1 Palenque Mataix, Elia
A1 Arnaiz Villena, Antonio
AB Gamma interferon (IFN-γ) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-γ receptor ligand-binding chain (IFN-γR1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-γR1 ligand-binding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN-γ (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN-γ receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.
PB American Society for Microbiology
SN 1098-6588
YR 2001
FD 2001-01-01
LK https://hdl.handle.net/20.500.14352/98102
UL https://hdl.handle.net/20.500.14352/98102
LA eng
NO Allende LM, López-Goyanes A, Paz-Artal E, Corell A, García-Pérez MA, Varela P, Scarpellini A, Negreira S, Palenque E, Arnaiz-Villena A. A point mutation in a domain of gamma interferon receptor 1 provokes severe immunodeficiency. Clin Diagn Lab Immunol. 2001 Jan;8(1):133-7. doi: 10.1128/CDLI.8.1.133-137.2001. PMID: 11139207; PMCID: PMC96022.
NO Ministerio de Educación y Ciencia
NO Comunidad Autónoma de Madrid
DS Docta Complutense
RD 6 abr 2025