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

Pediatr Blood Cancer. 2015 Jul;62(7):1288-90. doi: 10.1002/pbc.25483. Epub 2015 Mar 19.

Abstract

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.

Keywords: X-linked inhibitor of apoptosis; X-linked lymphoproliferative disease; hemophagocytic lymphohistiocytosis; skewed X chromosome inactivation.

Publication types

  • Case Reports

MeSH terms

  • Codon, Nonsense / genetics*
  • Female
  • Flow Cytometry
  • Genes, X-Linked / genetics*
  • Heterozygote*
  • Humans
  • Infant
  • Lymphohistiocytosis, Hemophagocytic / genetics*
  • Lymphohistiocytosis, Hemophagocytic / pathology
  • Male
  • Prognosis
  • X Chromosome Inactivation / genetics*
  • X-Linked Inhibitor of Apoptosis Protein / genetics*

Substances

  • Codon, Nonsense
  • X-Linked Inhibitor of Apoptosis Protein