Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis.
Astute Clinician Report: A Novel 10 bp Frameshift Deletion in Exon 2 of ICOS Causes a Combined Immunodeficiency Associated with an Enteritis and Hepatitis.
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DOI：
10.1007/s10875-015-0193-x
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发表时间：
2015-10
影响因子：
9.1
通讯作者：
Hambleton S
中科院分区：
文献类型：
--
作者：
Robertson N;Engelhardt KR;Morgan NV;Barge D;Cant AJ;Hughes SM;Abinun M;Xu Y;Koref MS;Arkwright PD;Hambleton S
ICOS编码可诱导T细胞共刺激因子（ICOS）。这种受体在人类中的缺乏引起常见的可变免疫缺陷（CVID），其特征在于缺乏类别转换记忆B细胞和低丙种球蛋白血症。迄今为止，在总共13例病例中描述了ICOS的三种致病性突变。在这里，我们报告了一个新的纯合10个碱基对移码缺失外显子2的全外显子组测序发现的两个兄弟姐妹从一个家庭的巴基斯坦血统。这两名患者都在儿童早期出现腹泻、结肠炎和转氨酶升高，其中一名患者表现出对人类疱疹病毒6的处理缺陷。活化的患者CD 3 + CD 4 + T淋巴细胞表现出完全不存在ICOS表达，与以前的报告一致，我们检测到循环T滤泡辅助细胞减少。这一家族的发现强调了ICOS缺乏症的表型变异性，特别是抗病毒免疫力受损，这是这种罕见疾病的一个知之甚少的方面。本文的在线版本（doi：10.1007/s10875-015-0193-x）包含补充材料，可供授权用户使用。
ICOS encodes the Inducible T-cell Co-Stimulator (ICOS). Deficiency of this receptor in humans causes a common variable immunodeficiency (CVID) characterised by an absence of class-switched memory B cells and hypogammaglobulinemia. Three pathogenic mutations in ICOS have been described to date in a total of 13 cases. Here we report a novel homozygous 10 base pair frameshift deletion in exon 2 discovered by whole exome sequencing of two siblings from a family of Pakistani origin. Both patients presented in early childhood with diarrhea, colitis and transaminitis and one showed defective handling of human herpesvirus 6. Activated patient CD3+CD4+ T lymphocytes demonstrated a complete absence of ICOS expression and, consistent with previous reports, we detected a reduction in circulating T follicular helper cells. Findings in this kindred emphasise the phenotypic variability of ICOS deficiency and, in particular, the variably impaired antiviral immunity that is a poorly understood facet of this rare disorder. The online version of this article (doi:10.1007/s10875-015-0193-x) contains supplementary material, which is available to authorized users.