| Summary: | Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal disease caused by uncontrolled proliferation of activated lymphocytes and macrophages. Six genes including SH2D1A, PRF1, UNC13D, STX11, STXBP2 and XIAP were reported as causative genes in most cases. Case presentation Here we report a novel splicing mutation in UNC13D gene, which was identified in an 18-year-old female. Patient was diagnosed as HLH base on HLH-2004 guidelines, no history of inherited diseases was revealed in this family, parents were healthy and non-consanguineous. Splenomegaly and hemophagocytosis in bone marrow were observed in clinical examination. Amplicon sequencing for the whole coding region of 6 HLH-related genes was performed on Ion S5XL genetic analyzer. In all, four heterozygous mutations were detected, including 2 nonpathogenic SNPs (PRF1:c.900C > T, STX11:c.*70G > A) and 2 splicing mutations in UNC13D gene (UNC13D:c.1299 + 1G > A and UNC13D:c.2709 + 1G > A), both of which were predicted to be potentially pathogenic by human splicing finder (HSF3) tool. The result was confirmed by two-generation pedigree analysis base on sanger sequencing. Conclusions Two compound heterozygous splicing mutations in UNC13D gene were identified and considered to be potential pathogenesis in a female patient of HLH. The mutation UNC13D:c.1299 + 1G > A was reported in HLH for the first time. The inheritance mode and source of the mutation in the proband was examined by family analysis. Our data suggest that further studies of the spectrum of HLH-related mutations in China are warranted.
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