Heterozygous IKKβ activation loop mutation results in a complex immunodeficiency syndrome

Jordan Abbott; Angelica C Ehler; Divya Jayaraman; Paul R Reynolds; Kanao Otsu; Laurie Manka; Erwin W Gelfand

doi:10.1016/j.jaci.2020.06.007

Heterozygous IKKβ activation loop mutation results in a complex immunodeficiency syndrome

J Allergy Clin Immunol. 2021 Feb;147(2):737-740.e6. doi: 10.1016/j.jaci.2020.06.007. Epub 2020 Jun 15.

Authors

Jordan Abbott¹, Angelica C Ehler², Divya Jayaraman³, Paul R Reynolds³, Kanao Otsu⁴, Laurie Manka⁴, Erwin W Gelfand³

Affiliations

¹ National Jewish Health, Immunodeficiency Diagnosis and Treatment Program, Department of Pediatrics, Denver, Colo; Section of Allergy and Immunology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colo; Children's Hospital of Colorado Aurora, Colo. Electronic address: Jordan.abbott@cuanschutz.edu.
² Section of Allergy and Immunology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colo; Children's Hospital of Colorado Aurora, Colo.
³ National Jewish Health, Immunodeficiency Diagnosis and Treatment Program, Department of Pediatrics, Denver, Colo.
⁴ Department of Medicine, National Jewish Health, Denver, Colo.

Abstract

We identified in an adult with ectodermal dysplasia and immunodeficiency a germline, gain-of-function mutation, K171R, in IKBKB. The K171R mouse immunologic phenotype parallels human, suggesting IKBKB K171R underlies a novel immunodeficiency syndrome.

Publication types

Case Reports
Letter
Research Support, N.I.H., Extramural

MeSH terms

Adult
Bronchiectasis
Fatal Outcome
Hemorrhage
Heterozygote
Humans
I-kappa B Kinase / genetics*
Immunologic Deficiency Syndromes / diagnosis*
Infections
Lung / pathology*
Male
Mutation / genetics*
Pedigree
Protein Conformation
Respiratory Insufficiency

Substances

I-kappa B Kinase
IKBKB protein, human

Grants and funding

K08 AI141734/AI/NIAID NIH HHS/United States