Hemophagocytic lymphohistiocytosis in a female patient due to a heterozygous XIAP mutation and skewed X chromosome inactivation

Genetic forms of hemophagocytic lymphohistiocytosis (HLH) are caused by mutations in autosomal recessive genes affecting perforin‐dependent cytotoxic function and two X‐linked genes affecting distinct cell signaling pathways: SH2D1A and XIAP . HLH caused by mutations in X‐linked genes is typically found only in males. Here we report the occurrence of HLH in a female caused by a heterozygous mutation in XIAP . Flow cytometric studies confirmed the absence of XIAP protein expression, while an X chromosome inactivation assay revealed an extreme skewing ratio of 99:1. This finding demonstrates that females are susceptible to X‐linked forms of HLH through skewed X chromosome inactivation. Pediatr Blood Cancer 2015;62:1288–1290. © 2015 Wiley Periodicals, Inc.