Abstract

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is an immune checkpoint, which downregulates T cell activation and T regulatory cell function. CTLA4 haploinsufficiency (CTLA4 HI) leads to T cell hyperactivation, immunodeficiency and variable degree of immune dysregulation. Furthermore, CTLA4 HI predisposes affected individuals to development of various cancers. Less well understood is the penetrance and expressivity of CTLA4 mutations. We describe five members of a single family with heterozygous CTLA4 splice site mutation c.458-1G > C, previously shown to result in CTLA-4 HI, who presented with immunodeficiency and variable degree of immune dysregulation. The host, environmental and the epigenetic factors affecting the penetrance and expressivity of CTLA4 mutations merits further investigation.

摘要

细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA4) 是一种免疫检查点，可下调 T 细胞活化和 T 调节细胞功能。CTLA4 单倍体不足 (CTLA4 HI) 导致 T 细胞过度活化、免疫缺陷和不同程度的免疫失调。此外，CTLA4 HI 使受影响的个体易患各种癌症。不太了解的是CTLA4突变的外显率和表达性。我们描述了具有杂合CTLA4剪接位点突变 c.458-1G > C的单个家族的五名成员，之前显示会导致 CTLA-4 HI，他们表现出免疫缺陷和不同程度的免疫失调。影响CTLA4外显率和表达性的宿主、环境和表观遗传因素突变值得进一步研究。