title: Hemophagocytic lymphohistiocytosis in a female patient due to a heterozygous XIAP mutation and skewed X chromosome inactivation.
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.
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Jennifer R
authors: JR
authors: Holle
authors: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Rebecca A
authors: RA
authors: Marsh
authors: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Anna Maria
authors: AM
authors: Holdcroft
authors: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Stella M
authors: SM
authors: Davies
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Lijun
authors: L
authors: Wang
authors: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Kejian
authors: K
authors: Zhang
authors: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.|Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Michael B
authors: MB
authors: Jordan
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D050172:Genes, X-Linked / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000473:pathology; D008297:Male; D011379:Prognosis; D049951:X Chromosome Inactivation / Q000235:genetics*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D051636:X-Linked Inhibitor of Apoptosis Protein
keywords: X-linked inhibitor of apoptosis; X-linked lymphoproliferative disease; hemophagocytic lymphohistiocytosis; skewed X chromosome inactivation