Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency.
Clin Exp Immunol
; 183(2): 221-9, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26437962
ABSTRACT
The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunodeficiência de Variável Comum
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Classe I de Fosfatidilinositol 3-Quinases
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Síndromes de Imunodeficiência
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Mutação
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Exp Immunol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha