Familial hemophagocytic lymphohistiocytosis (FHL) is a rare and life-threatening autosomal recessively inherited disorder that results from the uncontrolled proliferation or over activation of T-lymphocyte and macrophage, over production of inflammatory cytokines and immune dysregulation. Untreated patients have a death rate of around 95%, which can only be reversed through immunochemotherapy and hematopoietic stem cell transplantation. Mutations in genes STX11, STXBP2, UNC13D, and PRF1 are represent the most common causes in the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). FHL can be classified into five categories based on the disease-causing mutations in genes involved in NK and T-cell granule-mediated cytotoxicity. Here, we reported a homozygous mutation in UNC13D gene in a 4-month-old boy suffering with fever, pancytopenia, splenomegaly, hypertriglyceridemia and, suspected with hemophagocytosis. The boy, presented with typical symptoms and required criteria for the diagnosis with HLH based on HLH-2004 guidelines. A novel homozygous frameshift deletion mutation in UNC13D gene (c.3061_3067delCCGCTGC;p.Pro1021ValfsTer6) was detected by whole exome sequencing (WES) in the proband which was later confirmed by Sanger sequencing. The present study is believed to be the first one in the context HLH in Indian population.

Keywords: UNC13D; Familial Hemophagocytic Lymphohistiocytosis (FLH); Whole Exome Sequencing; Frameshift mutation; HLH