A Female Patient with Incomplete Hemophagocytic Lymphohistiocytosis Caused by a Heterozygous XIAP Mutation Associated with Non-Random X-Chromosome Inactivation Skewed Towards the Wild-Type XIAP Allele

作者：Yang Xi; Hoshino Akihiro; Taga Takashi; Kunitsu Tomoaki; Ikeda Yuhachi; Yasumi Takahiro; Yoshida Kenichi; Wada Taizo; Miyake Kunio; Kubota Takeo; Okuno Yusuke; Muramatsu Hideki; Adachi Yuichi; Miyano Satoru; Ogawa Seishi; Kojima Seiji; Kanegane Hirokazu^*

来源：Journal of Clinical Immunology, 2015, 35(3): 244-248.

DOI：10.1007/s10875-015-0144-6

• Hemophagocytic lymphohistiocytosis
• X-chromosome inactivation
• X-linked inhibitor of apoptosis
• X-linked lymphoproliferative syndrome

X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency that often leads to hemophagocytic lymphohistiocytosis (HLH). XLP can be classified as XLP1 or XLP2, caused by mutations in SH2D1A and XIAP, respectively. In women, X-chromosome inactivation (XCI) of most X-linked genes occurs on one of the X chromosomes in each cell. The choice of which X chromosome remains activated is generally random, although genetic differences and selective advantage may cause one of the X chromosomes to be preferentially inactivated. Here we describe three patients with pancytopenia, including one female patient, in a Japanese family with a novel XIAP mutation. All three patients exhibited deficient XIAP protein expression, impaired NOD2/XIAP signaling, and augmented activation-induced cell death. In the female patient, the paternally derived X chromosome was non-randomly and exclusively inactivated in her peripheral blood and hair root cells. In contrast to asymptomatic females, this patient exhibied non-random XCI skewed towards the wild-type XIAP allele. This is the first report of a female patient with incomplete HLH resulting from a heterozygous XIAP mutation in association with non-random XCI.

• 出版日期2015-4
• 单位河北医科大学