Perforin-1 does not appear to be associated with familial hematological malignancies.Reportar como inadecuado

Perforin-1 does not appear to be associated with familial hematological malignancies. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 UR Biologie moléculaire des leucémies et lymphomes - Faculté de Médecine de Sousse 2 Service d-Oncologie Génétique, de Prévention et Dépistage 3 Cancer Cell Death Laboratory 4 Service d-Hématologie Clinique 5 Centre Antoine Lacassagne 6 CHG Niort 7 Polyclinique de Courlancy 8 Institut Ste Catherine 9 Unité de génétique Epidémiologique 10 CRLCC - CRLCC Eugène Marquis 11 Département de Génétique 12 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs CHU de Dijon 13 Service d-oncogénétique Centre georges-François Leclerc 14 Centre régional de transfusion sanguine de Sousse 15 Université de la Méditerranée - Aix-Marseille 2

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.

keyword : PRF1 germline mutation hematological familial malignancies

Autor: Rim El Abed - Violaine Bourdon - Ilia Voskoboinik - Halima Omri - Yosra Youssef - Mohamed Laatiri - Laetitia Huiart - François E



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