The role of cxcr4 genes mutation in familial hemophagocytic lymhohistiocytosis (HLH)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by immune irregularity. HLH is called as primary or familial hemophagocytic lymphohistiocytosis (FHL) when there is a familial history or genetic defects. FHL is an autosomal disorder that is caused by immune disorders. It is exactly known that genetic defects in HLH disease that impair lytic processes in cytolytic secretory pathway. Chemokines are proinflammatory chemoattractant cytokines. Chemokines play major roles in pathophysiological conditions like angiogenesis, hematopoiesis, embryogenesis, atherosclerosis, HIV infections and cancer. IL-1ß, TNF-?, lipopolysaccharides (LPS), some growth factors, viral infection and bacterial products are important stimulatory factors for chemokines. In this thesis study, mutational screning was performed in the exon regions of CXCR4 gene that is chemokine receptor in patients with FHL. Firstly, the exon regions of CXCR4 gene was amplified with Polymerase Chain Reaction (PCR) by using DNA samples obtained from blood of FHL patients. After PCR step, mutational screening of the exon regions of CXCR4 gene for each patients was done by agarose gel electrophoresis and automated nucleotide sequencing device. According to the results of DNA sequencing of CXCR4 gene, the deletion of F174 (174. Phenylalanine in 2. exon of CXCR4 gene) was identified in two patients with familial HLH. These results suggest that mutations occurring on chemokine receptor CXCR4 in familial HLH disease need to be evaluated further and perhaps should be taken into consideration. Key words: CXCR4, FHL, HLH, mutational screening, sequencing analysis