Журнал генетических синдромов и генной терапии
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Identification of a Deletion in Stxbp2 Causative of Familial Hemophagocytic Lymphohistiocytosis Type

Coniglio ML, Cetica V, Ciambotti B, Grieve S, Pantaleo M, Rizzari C, Sieni E, Favre C, Giglio S, Griffiths GM and Arico M

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening immune deficiency, characterized by a hyper-inflammatory syndrome. The familial form of HLH (FHL) is caused by mutations in genes associated with lymphocyte granule-mediated cytotoxicity. Mutations in STXBP2 (Sintaxin binding protein 2) gene result in defect of Munc18-2 protein, the causative defect of the subtype defined as FHL5. Functional tests as intracytoplasmic expression of perforin and surface expression of CD107a, help to direct genetic analysis. Different mutations have been described in the FHL-related genes known so far (PRF1, UNC13-D, STX11, STXBP2): missense, nonsense, splicing, regulatory, small deletions/insertions. Recently a pathogenic inversion of 253 KB upstream of the 3’ UNC13D gene has been reported. Here we describe a new deletion causative of FHL5. We confirmed the deletion by Real-Time PCR and by CGHarray. We finally documented by western blot the absence of expression of Munc18-2 protein in our patient. These data shows the need to introduce new diagnostic strategies in order to screen mutations not detected by the methods classically used.