Familial hemophagocytic lymphohistiocytosis associated gene mutations in Chinese lymphoma patients with human herpes virus infection

Abstract

Objective To investigate the association of mutations in genes associated with familial hemophagocytic lymphohistiocytosis(FHL)and lymphoma with active human herpes virus(HHV)infection in Chinese patients. Methods Patients with either Hodgkin or non-Hodgkin lymphomas and active HHV infection were enrolled in. Active HHV1-8 infections were tested by PCR method. PCR amplification and Sanger sequencing for UNC13D, PRF1, STXBP2, STX11, SH2D1A, and XIAP were performed. Results 59 patients were collected(age, 3-60 years), including 33 males and 26 females. Mutations were observed in 15 patients(25.42 %). 10 patients carried mutations in UNC13D, including 7 cases with monoallelic mutations, 1 case with homozygous mutation and 2 cases with compound heterozygous mutations. 4 patients had PRF1 mutations, including 1 case with monoallelic mutation, 1 case with homozygous mutation and 2 cases with compound heterozygous mutations. 1 patient was detected to carry STX11 monoallelic mutation. All mutations were confirmed to be germline derived by pedigree analysis or sequencing of non-lymphoma tissue of the same patient. Conclusions A proportion of patients with HHV-lymphoma may harbor mutations of the FHL associated genes, which are probably the innate predisposing factors of active HHV infection and lymphomagenesis. Key words: Familial hemophagocytic lymphohistiocytosis; Lymphoma; Gene mutation; Human herpes virus