Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1

Frontiers in Pediatrics

article

Panida Sriaroon¹  Yenhui Chang²  Boglarka Ujhazi¹  Krisztian Csomos¹  Hemant R. Joshi³  Qin Zhou³  Devin W. Close⁴  Jolan E. Walter¹  Attila Kumánovics³ 

[1] Division of Allergy, Department of Pediatrics, University of South Florida Morsani College of Medicine, United States;Pathology and Laboratory Medicine, Johns Hopkins All Children's Hospital, United States;Department of Pathology, University of Utah School of Medicine, United States;ARUP Laboratories, Institute for Clinical and Experimental Pathology, United States;Division of Allergy/Immunology, Massachusetts General Hospital for Children, United States;Department of Laboratory Medicine and Pathology, Mayo Clinic, United States

关键词: primary immunodeficiency;    autoimmunity;    immune thrombocytopenia;    ITP;    IKAROS deficiency;    IKZF1;   

DOI  :  10.3389/fped.2019.00139

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

We report a novel variant in IKZF1 associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the IKZF1 gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified IKZF1 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.

【 授权许可】

CC BY