Perforin and STX11 effect in (FHL) familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disorder caused by immune dysregulation with hypercytokinemia (cytokine storm) which leads to a defective natural killer cell (NK) and cytotoxic T lymphocyte (CTL) development. This is severe and fatal syndrome because of uncontrolled activation and proliferation of Tlymphocytes. Mutations in perforin (PRF1, FHL 2), Munc13-4 (UNC14D, FHL3) and SINTAX 11 (STX11, FHL 4) genes cause Familial Hemophagocytic Lymphohistiocytosis disease. Genomic DNA of 14 patients was obtained from their peripheral blood by using standart salting out DNA isolation technique. Primer designs of perforin and syntaxin genes were made to analyze the exons of both genes. After amplification of exonic region of STX11 and perforin genes, mutational screening of STX11 and perforin genes was done using automatic sequence analysis. Mutational and nucleotide sequence analysis of the exons revealed three mutations found in three patients in their perforin and syntaxin 11 genes. In one patient, AG and CGC nucleotide sequence deletions of second exon of STX11 gene was detected. In the second patient, CAC? CAT exchange was identified in the third exon of perforin gene. In the third patient, insertion of 7 nucleotide sequences (TACTGAC) was detected in the third exon of perforin gene. Molecular analysis plays an important role in the diagnosis of Familial Hemophagocytic Lymphohistiocytosis (FHL) disease. Detection of perforin and STX11 mutations deserve importance in this respect. Key words: FHL, gene sequencing, Perforin variant, STX11 variants, mutational screening