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Open Access 01-12-2011 | Research

Molecular study of the perforin gene in familial hematological malignancies

Authors: Rim El Abed, Violaine Bourdon, Ilia Voskoboinik, Halima Omri, Yosra Ben Youssef, Mohamed Adnene Laatiri, Laetitia Huiart, François Eisinger, Laetitia Rabayrol, Marc Frenay, Paul Gesta, Liliane Demange, Hélène Dreyfus, Valérie Bonadona, Catherine Dugast, Hélène Zattara, Laurence Faivre, Monia Zaier, Saloua Yacoub Jemni, Testsuro Noguchi, Hagay Sobol, Zohra Soua

Published in: Hereditary Cancer in Clinical Practice | Issue 1/2011

Abstract

Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein.

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Title: Molecular study of the perforin gene in familial hematological malignancies
Authors: Rim El Abed
Violaine Bourdon
Ilia Voskoboinik
Halima Omri
Yosra Ben Youssef
Mohamed Adnene Laatiri
Laetitia Huiart
François Eisinger
Laetitia Rabayrol
Marc Frenay
Paul Gesta
Liliane Demange
Hélène Dreyfus
Valérie Bonadona
Catherine Dugast
Hélène Zattara
Laurence Faivre
Monia Zaier
Saloua Yacoub Jemni
Testsuro Noguchi
Hagay Sobol
Zohra Soua
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Hereditary Cancer in Clinical Practice / Issue 1/2011
Electronic ISSN: 1897-4287
DOI: https://doi.org/10.1186/1897-4287-9-9

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