<i>PTPN1</i> -related autoinflammation is a common cause of Aicardi-Goutières Syndrome with reduced penetrance
Purpose: is a negative regulator of the interferon pathway previously associated with chronic inflammation and recently type 1 IFN autoinflammation. Methods: database. Results: database, none had features suggestive of AGS, but autoimmunity was highly prevalent (~21.6%). Conclusion: as a cause of later-onset presentations of AGS within a broader spectrum of autoinflammatory phenotypes. Segregation and biobank data demonstrate reduced penetrance, with carriers being enriched for autoimmune disorders.
Authors
- Raphael Schiffmann (ORCID: https://orcid.org/0000-0003-2437-0252)
- Jennifer E. Posey (ORCID: https://orcid.org/0000-0003-4814-6765)
- Milena M. Andzelm (ORCID: https://orcid.org/0000-0002-9189-1691)
- Cas Simons (ORCID: https://orcid.org/0000-0003-3147-8042)
- Rauan B. Kaiyrzhanov (ORCID: https://orcid.org/0000-0003-1640-4010)
- Matthew T. Whitehead (ORCID: https://orcid.org/0000-0001-5077-693X)
- Asako Takanohashi (ORCID: https://orcid.org/0000-0003-3292-1595)
- Anjana Sevagamoorthy (ORCID: https://orcid.org/0000-0002-9212-2501)
- Mira Gandhi
- Quinten Waisfisz (ORCID: https://orcid.org/0000-0002-7384-9182)
- S. Jhangiani
- Daniel G. Calame (ORCID: https://orcid.org/0000-0001-6860-372X)
- Donna M. Muzny (ORCID: https://orcid.org/0000-0002-3055-0359)
- Kristen S. Fisher (ORCID: https://orcid.org/0000-0002-1598-8571)
- Catherine Otten (ORCID: https://orcid.org/0000-0003-1618-9437)
- J.M.F. Niermeijer
- Danielle DeMarzo
- Stephen C. Wong (ORCID: https://orcid.org/0000-0003-1617-9634)
- Heer H. Mehta (ORCID: https://orcid.org/0000-0002-5357-2112)
- Francesco Gavazzi (ORCID: https://orcid.org/0000-0002-4908-8395)
- Tejas Jammihal (ORCID: https://orcid.org/0000-0003-4614-1266)
- Henry Houlden (ORCID: https://orcid.org/0000-0002-2866-7777)
- Reza Maroofian (ORCID: https://orcid.org/0000-0001-6763-1542)
- Emma K. Wiener (ORCID: https://orcid.org/0000-0001-9184-0264)
- Moez Dawood (ORCID: https://orcid.org/0000-0003-0192-1277)
- Nicole I. Wolf (ORCID: https://orcid.org/0000-0003-0830-4626)
- J.R. Lupski
- Kaley Arnold
- Edward Formaini
- Jesse Levine
- Sara Woidill
- Janhavi Lele
- Amy Pizzino
- Lisa Emrick
- Kathleen E. Sullivan
- Ivan K Chinn
- Adeline Vanderver
- Darius Ebrahimi-Fakhari
- Laura Adang
- Chadi Al Alam
- Thomas Reynolds
- Rocio Rius
- Russell D'Aiello
- Ramakrishnan Rajagopalan
- Arastoo Vossough
- Mariko Bennett
- Richard A. Gibbs
- Fritz J Sedlazeck
Institutions
- Tufts University (US)
- Boston Children's Hospital (US)
- Texas Christian University (US)
- Children's Hospital of Philadelphia (US)
- Garvan Institute of Medical Research (AU)
- Baylor College of Medicine (US)
- Scarborough General Hospital (GB)
- New England Cancer Specialists (US)
- MaineHealth (US)
- Amsterdam Neuroscience (NL)
- Seattle Children's Hospital (US)
- Neurological Research Institute (US)
- Texas Children's Hospital (US)
- Elisabeth-TweeSteden Ziekenhuis (NL)
- Murdoch Children's Research Institute (AU)
- Barbara Bush Children’s Hospital (US)
- University College London (GB)
- University of Pennsylvania (US)
- University of Oklahoma (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-04-01
- DOI
- https://doi.org/10.64898/2026.03.27.26345228
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Eli Lilly and Company
- Sanofi
- Biogen
- Children's Hospital of Philadelphia
- Ionis Pharmaceuticals
- National Institutes of Health
- National Human Genome Research Institute
- National Institute of Neurological Disorders and Stroke