Mouse Anti-Human Perforin monoclonal antibody, clone JID757

Background: Familial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16-40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature. Methods: In the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation. Results: Nineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53. Conclusions: In this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population.

Hemophagocytic lymphohistiocytosis (HLH) is a multisystem inflammatory disorder due to cytokine overproduction from excessively activated lymphocytes and macrophages. HLH has been divided into two subgroups: primary HLH and secondary HLH. Primary HLH includes PRF1, UNC13D, STX11, STXBP2, RAB27A, LYST, SH2D1A and XIAP gene mutations; and secondary HLH is associated with infections, malignancies and autoimmune diseases. Among primary HLH-related genes, SH2D1A and XIAP are genetically responsible for X-linked lymphoproliferative syndrome (XLP) due to signaling-lymphocytic-activation-molecule-associated protein (SAP) and XIAP deficiencies, respectively. XLP is characterized by extreme vulnerability to EpsteinBarr virus infection. The major clinical manifestations of XLP consist of HLH (60%), lymphoproliferative disorder (30%) and dysgammaglobulinemia (30%). Analysis of clinical phenotypes of XLP patients suggests that XLP predominantly shows familial HLH phenotypes, whereas some XLP patients present sporadic HLH. For many decades, clinicians and investigators have been concerned with possible XLP in young boys presenting with EpsteinBarr-virus-associated HLH. This review aims to describe the new knowledge about XLP and to draw the attention of the pediatrician to XLP, which should be differentiated from other forms of HLH.