Functional impact of A91V mutation of the PRF1 perforin gene.
Hum Immunol
; 74(1): 14-7, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23073290
ABSTRACT
Perforin (PRF1) gene mutations have been associated with Familial Hemophagocytic Lymphohistiocytosis type 2 (FHL2). Substitution p.A91V (c.272C>T) in exon 2 was first described as a neutral polymorphism. Nonetheless, recent clinical evidence and functional assays, suggest a potential pathogenic role for p.A91V, especially in compound heterozygous individuals. Moreover, p.A91V homozygosity has been linked to various pathological states including FHL and lymphocytic leukaemias. In the present report we evaluated the impact of this mutation in a compound heterozygous A91V/G149S 31 year-old asymptomatic female. Functional assays revealed low perforin expression levels, as well as an impaired NK cell-mediated cytotoxicity, partially reconstituted after incubation with IL-2. These results support that p.A91V mutation, associated to another mutated PRF1 allele, may potentially predispose seemingly healthy carriers to suffer a milder FHL2 clinical phenotype, including later onset of the disease. Thus, clinical monitoring of p.A91V carrier individuals bearing another mutation in PRF1 is warranted.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Linfo-Histiocitose Hemofagocítica
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Proteínas Citotóxicas Formadoras de Poros
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Mutação
Tipo de estudo:
Diagnostic_studies
Limite:
Adult
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Female
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article