Gain-of-function variants in <i>IRF6</i> cause hidradenitis suppurativa, ectodermal dysplasia and deafness syndrome
We report two gain-of-function IRF6 variants (p.Ile218_Ser220delinsSerSerGlyAla; p.Ile218Asn) as the genetic basis of early-onset hidradenitis suppurativa, ectodermal dysplasia and deafness (HSEDD) – a novel syndrome expanding IRF6-related disorders beyond developmental phenotypes. These variants constitutively hyperactivate IL-1β and IFN pathways in keratinocytes and patient tissues. This work establishes IRF6-driven autoinflammation as a therapeutic target for HSEDD and related skin disorders.
Authors
- Zhimiao Lin (ORCID: https://orcid.org/0000-0002-3240-1998)
- Sha Peng
- Shuang Zhao (ORCID: https://orcid.org/0000-0001-7081-6177)
- Gaolei Zhang (ORCID: https://orcid.org/0000-0003-4451-7864)
- Zeqiao Zhang (ORCID: https://orcid.org/0000-0003-0333-9512)
- Zhiqi Yan (ORCID: https://orcid.org/0000-0003-0402-5929)
- Huijun Wang (ORCID: https://orcid.org/0000-0001-5414-1472)
- Yaxuan Lv
- Kunlun Lv
Institutions
- Beijing Children’s Hospital (CN)
- Southern Medical University (CN)
Publication Details
- Journal
- British Journal of Dermatology
- Published
- 2025-10-03
- DOI
- https://doi.org/10.1093/bjd/ljaf390
- Primary Topic
- Hidradenitis Suppurativa and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00