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BioMed Central, Hereditary Cancer in Clinical Practice, 1(9), 2011

DOI: 10.1186/1897-4287-9-9

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Molecular study of the perforin gene in familial hematological malignancies

Journal article published in 2011 by Rim El Abed, Hélène Zattara, Monia Zaier, Violaine Bourdon, Ilia Voskoboinik ORCID, Halima Omri, Yosra Ben Youssef, Mohamed Adnene Laatiri, Paul Gesta, Laetitia Huiart, Liliane Demange, François Eisinger, Hélène Dreyfus, Valérie Bonadona, Laetitia Rabayrol and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.