Sriaroon Panida, Chang Yenhui, Ujhazi Boglarka, Csomos Krisztian, Joshi Hemant R, Zhou Qin, Close Devin W, Walter Jolan E, Kumánovics Attila
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of South Florida Morsani College of Medicine, St. Petersburg, FL, United States.
Pathology and Laboratory Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
Front Pediatr. 2019 Apr 24;7:139. doi: 10.3389/fped.2019.00139. eCollection 2019.
We report a novel variant in associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified variant (p.His195Arg) alters a completely conserved histidine residue required for the folding of the third zinc-finger of IKAROS protein, leading to a loss of characteristic immunofluorescence nuclear staining pattern. In our case, genetic testing was essential for the diagnosis of IKAROS haploinsufficiency, of which known presentations include infections, aberrant hematopoiesis, leukemia, and age-related decrease in humoral immunity. Our family study underscores that, after infections, ITP is the second most common clinical manifestation of IKAROS haploinsufficiency.
我们报告了1例家族性免疫性血小板减少症（ITP）患者中与IKAROS单倍体不足相关的一种新型变异。IKAROS由IKZF1基因编码，是一种造血锌指转录因子，可直接与DNA结合。我们发现，鉴定出的IKZF1变异（p.His195Arg）改变了IKAROS蛋白第三个锌指折叠所需的一个完全保守的组氨酸残基，导致特征性免疫荧光核染色模式丧失。在我们的病例中，基因检测对于IKAROS单倍体不足的诊断至关重要，其已知表现包括感染、异常造血、白血病以及与年龄相关的体液免疫下降。我们的家族研究强调，感染后，ITP是IKAROS单倍体不足的第二常见临床表现。
