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Inborn errors of human IKAROS: LOF and GOF variants associated with primary immunodeficiency.

Hye Sun KuehnBrigette BoastSergio D Rosenzweig
Published in: Clinical and experimental immunology (2022)
IKAROS/IKZF1 plays a pivotal role in lymphocyte differentiation and development. Germline mutations in IKZF1, which have been shown to associated with primary immunodeficiency, can be classified through four different mechanisms of action depending on the protein expression and its functional defects: haploinsufficiency, dimerization defective, dominant negative, and gain-of-function. These different mechanisms are associated with variable degrees of susceptibility to infectious diseases, autoimmune disorders, allergic diseases, and malignancies. To date, more than 30 heterozygous IKZF1 germline variants have been reported in patients with primary immunodeficiency. Here we review recent discoveries and clinical/immunological characterization of IKAROS-associated disorders that are linked to different mechanisms of action in IKAROS function.
Keyphrases
  • acute lymphoblastic leukemia
  • infectious diseases
  • copy number
  • endothelial cells
  • dna repair
  • dna methylation
  • gene expression
  • induced pluripotent stem cells
  • adverse drug
  • oxidative stress
  • quality improvement