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Hemophagocytic lymphohistiocytosis in a female patient due to a heterozygous XIAP mutation and skewed X chromosome inactivation
Author(s) -
Holle Jennifer R.,
Marsh Rebecca A.,
Holdcroft Anna Maria,
Davies Stella M.,
Wang Lijun,
Zhang Kejian,
Jordan Michael B.
Publication year - 2015
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.25483
Subject(s) - xiap , hemophagocytic lymphohistiocytosis , mutation , x chromosome , x inactivation , gene , genetics , perforin , cancer research , chromosome , skewed x inactivation , cytotoxic t cell , medicine , biology , microbiology and biotechnology , apoptosis , programmed cell death , disease , caspase , in vitro
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.