A novel intronic splice site deletion of the IL-2 receptor common gamma chain results in expression of a dysfunctional protein and T-cell-positive X-linked Severe combined immunodeficiency.
Int J Immunogenet
; 42(1): 11-4, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25443657
ABSTRACT
X-linked severe combined immunodeficiency is caused by mutations in the IL-2 receptor common gamma chain and classically presents in the first 6 months of life with predisposition to bacterial, viral and fungal infections. In most instances, affected individuals are lymphopenic with near complete absence of T cells and NK cells. We report a boy who presented at 12 months of age with Pneumocystis jiroveci pneumonia and a family history consistent with X-linked recessive inheritance. He had a normal lymphocyte count including the presence of T cells and a broad T-cell-receptor diversity, as well as normal surface expression of the common gamma chain (CD132) protein. He however had profound hypogammaglobulinaemia, and IL-2-induced STAT5 phosphorylation was absent. Sequencing of IL-2RG demonstrated a 12-base pair intronic deletion close to the canonical splice site of exon 5, which resulted in a variety of truncated IL2RG mRNA species. A review of the literature identified 4 other patients with T-cell-positive X-SCID, with the current patient being the first associated with an mRNA splicing defect. This case raises the question of how a dysfunctional protein incapable of mediating STAT5 phosphorylation might nonetheless support T-cell development. Possible explanations are that STAT5-mediated signal transduction may be less relevant to IL7-receptor-mediated T-cell development than are other IL7R-induced intracellular transduction pathways or that a low level of STAT5 phosphorylation, undetectable in the laboratory, may be sufficient to support some T-cell development.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neumonía por Pneumocystis
/
Eliminación de Secuencia
/
Agammaglobulinemia
/
Enfermedades Genéticas Ligadas al Cromosoma X
/
Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X
/
Subunidad gamma Común de Receptores de Interleucina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Int J Immunogenet
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
GENETICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Australia