EDA-ID: a Severe Clinical Presentation Associated with a New IKBKG Mutation

This is a preview of subscription content, access via your institution.

Fig. 1





Ectodermal dysplasia with immunodeficiency


Graft-versus-host disease


Human leukocyte antigen


Hematopoietic stem cell transplantation


NF-κB essential modulator


  1. 1.

    Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israël A, Courtois G, Casanova JL X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling. Nat Genet. mars 2001; https://doi.org/10.1038/85837.

  2. 2.

    Miot C, Imai K, Imai C, Mancini AJ, Kucuk ZY, Kawai T, et al. Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations. Blood. 2017. https://doi.org/10.1182/blood-2017-03-771600.

  3. 3.

    Boisson B, Honda Y, Ajiro M, Bustamante J, Bendavid M, Gennery AR, et al. Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency. J Clin Invest. 2019;129(2):583–97. https://doi.org/10.1172/JCI124011.

    Article  PubMed  Google Scholar 

  4. 4.

    Peggs KS, Verfuerth S, Pizzey A, Khan N, Guiver M, Moss PA, et al. Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. The Lancet. 2003. https://doi.org/10.1016/S0140-6736(03)14634-X.

  5. 5.

    Fusco F, Pescatore A, Conte MI, Mirabelli P, Paciolla M, Esposito E, et al. EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-κB pathway can cause immunodeficiency and/or inflammation. Int Rev Immunol. 2015;34(6):445–59.

    CAS  Article  Google Scholar 

  6. 6.

    Gibson DC, Couser NL, King KB. Co-occurrence of incontinentia pigmenti and down syndrome: examining patients’ potential susceptibility to autoimmune disease, autoinflammatory disease, cancer, and significant ocular disease. Ophthalmic Genet. Taylor & Francis. 2020:1–4. https://doi.org/10.1080/13816810.2020.1839917.

  7. 7.

    Elsarraj HS, Valdez KE, Hong Y, Grimm SL, Ricci LR, Fan F, et al. NEMO, a transcriptional target of estrogen and progesterone, is linked to tumor suppressor PML in breast cancer. Cancer Res 15. 2017;77(14):3802–13.

    CAS  Article  Google Scholar 

  8. 8.

    Hanson EP, Monaco-Shawver L, Solt LA, Madge LA, Banerjee PP, May MJ, et al. Hypomorphic nuclear factor-κB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. J Allergy Clin Immunol. Elsevier. 2008;122(6):1169–1177.e16.

    CAS  Article  Google Scholar 

Download references


The authors would like to thank Christophe Malcus (Immunology Lab) and Linda Pons (Department of Genetics) from Hospices Civils de Lyon (France, EU) for their help in the conception of this article. They also thank Patrick Combemale who diagnosed IP in the mother and reviewed the manuscript (Oncology and dermatology unit, Léon Bérard center, Lyon, France, EU). Finally, they thanked the parents for agreeing to this case report.

Author information




I (Coline Bret Puvilland) collected the data, studied the literature and wrote the manuscript. Mathieu Fusaro, Bertrand Boisson, and Jacinta Bustamante performed the NGS analyses, performed the experiments, and reviewed the manuscript. Marie Ouachée-Chardin and Yves Bertrand were the hematologists in charge of the patient, conducted the medical follow-up, and reviewed the manuscript. Antony Ceraulo was the hematologist in charge of the patient, helped collecting the data, helped writing the manuscript, and provided expertise and critical reading. All authors contributed to the study conception and design. All authors read and approved the final manuscript, and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Coline Bret Puvilland.

Ethics declarations

Ethics approval

Our local ethics committee approved this study.

Consent to Participate

Verbal informed consent was obtained from parents.

Conflict of Interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information


Evolution of the CMV plasmatic viral load (Artus kit CMV QS-RGS, Qiagen®) and treatments (PDF 140 kb)


Immunological characteristics of the patient (PDF 217 kb)


Methods of functional characterization of the variant (PDF 224 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bret Puvilland, C., Boisson, B., Fusaro, M. et al. EDA-ID: a Severe Clinical Presentation Associated with a New IKBKG Mutation. J Clin Immunol (2021). https://doi.org/10.1007/s10875-021-00992-x

Download citation