Identification of a novel IRF8 homozygous mutation causing neutrophilia, monocytopenia and fatal infection in a female neonate
Identification of a novel IRF8 homozygous mutation causing neutrophilia, monocytopenia and fatal infection in a female neonate
复制标题
DOI：
10.1016/j.meegid.2021.105121
复制
发表时间：
2021-10-20
影响因子：
3.2
通讯作者：
Wu, Hui
中科院分区：
文献类型：
--
作者：
Dang, Dan;Liu, Ying;Wu, Hui
先天性免疫缺陷（IEIs）是由参与宿主免疫防御和免疫调节的基因突变引起的。在此，我们报告了一个新的IRF 8突变的新生儿IEI的鉴定。对新生儿及其父母的DNA样本进行DNA测序，并评估患者的免疫状态。我们在干扰素调节因子8（IRF 8）基因中发现了一个突变（c.331C > T，p.Arg111 *），表现为严重功能失调性嗜中性粒细胞增多症（96.53 x 109/l）和单核细胞减少症（0.02 x 109/l）。患者的CD 3 + T细胞和CD 8 + T细胞计数降低。即使在严重感染期间，她的IFN-γ水平也很低。IRF 8的mRNA表达水平低于正常。她的临床表现包括反复发作和进行性致命感染。由于IRF 8在免疫细胞的分化和发育中起关键作用，我们怀疑新突变（c.331C > T，p.Arg111 *）可能与IRF 8功能的严重丧失一致，导致免疫细胞分化和成熟失败，并导致早期发作的严重感染。
Inborn errors of immunity (IEIs) result from mutations in genes involved in host immune defense and immune regulation. Herein, we report the identification of a novel IRF8 mutation in a neonate with an IEI. DNA samples from both the neonate and her parents were subjected to DNA sequencing, and the immune status of the patient was assessed. We identified a mutation (c.331C > T, p. Arg111*) in the interferon regulatory factor 8 (IRF8) gene that manifested as sever dysfunctional neutrophilia (96.53 x 109/l) and monocytopenia (0.02 x 109/l). The patient's CD3+ T cell and CD8+ T cell counts were decreased. Her levels of IFN-gamma were low even during severe infection. The mRNA expression levels of IRF8 were lower than normal. Her clinical manifestations included a recurrent and progressively fatal infection. Since IRF8 plays a key role in the differentiation and development of immune cells, we suspected that the novel mutation (c.331C > T, p. Arg111*) may be consistent with a severe loss of IRF8 function and result in a failure of immune cells to differentiate and maturation, and lead to a severe infection with early onset.