Department of Pediatric Hematology Oncology and BMT, Cleveland Clinic Children's, Cleveland, Ohio, USA.
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Children's, Cleveland, Ohio, USA.
Pediatr Hematol Oncol. 2021 Oct;38(7):658-662. doi: 10.1080/08880018.2021.1906802. Epub 2021 Apr 26.
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 mutations. We describe five members of a single family with heterozygous 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 mutations merits further investigation.
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 细胞激活和 T 调节细胞功能。CTLA4 杂合不足（CTLA4 HI）导致 T 细胞过度激活、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。不太清楚的是突变的外显率和表现度。我们描述了一个具有杂合性剪接位点突变 c.458-1G>C 的单一家庭的五名成员，该突变先前被证明导致 CTLA-4 HI，他们表现出免疫缺陷和不同程度的免疫失调。影响突变外显率和表现度的宿主、环境和表观遗传因素值得进一步研究。
