Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Pediatr Blood Cancer. 2015 Jul;62(7):1288-90. doi: 10.1002/pbc.25483. Epub 2015 Mar 19.
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.
遗传性噬血细胞性淋巴组织细胞增生症（HLH）是由常染色体隐性基因突变引起的，这些突变影响穿孔素依赖性细胞毒性功能，以及影响两条 X 连锁基因的不同细胞信号通路：SH2D1A 和 XIAP。X 连锁基因突变引起的 HLH 通常仅见于男性。在此，我们报告了一例由 XIAP 杂合突变引起的女性 HLH 病例。流式细胞术研究证实 XIAP 蛋白表达缺失，而 X 染色体失活分析显示出极端的偏倚比 99:1。这一发现表明，女性通过 X 染色体失活的偏倚而易患 X 连锁形式的 HLH。
