Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype

Author:

Toubiana Julie1234ORCID,Okada Satoshi56ORCID,Hiller Julia78,Oleastro Matias9,Lagos Gomez Macarena10,Aldave Becerra Juan Carlos11,Ouachée-Chardin Marie12,Fouyssac Fanny13,Girisha Katta Mohan14,Etzioni Amos15,Van Montfrans Joris16,Camcioglu Yildiz17,Kerns Leigh Ann18,Belohradsky Bernd19,Blanche Stéphane24,Bousfiha Aziz20,Rodriguez-Gallego Carlos21,Meyts Isabelle22,Kisand Kai23,Reichenbach Janine24,Renner Ellen D.19,Rosenzweig Sergio25,Grimbacher Bodo26,van de Veerdonk Frank L.27,Traidl-Hoffmann Claudia78,Picard Capucine23428,Marodi Laszlo29,Morio Tomohiro30,Kobayashi Masao6,Lilic Desa31,Milner Joshua D.32,Holland Steven25,Casanova Jean-Laurent23533,Puel Anne23534ORCID

Affiliation:

1. Department of General Pediatrics and Pediatric Infectious Diseases, Assistance Publique-Hôpitaux de Paris (AP-HP), Necker-Enfants Malades Hospital, Paris, France;

2. Paris Descartes University, Sorbonne Paris Cité, Institut Imagine, Paris, France;

3. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Necker Medical School, Paris, France;

4. Pediatric Hematology-Immunology-Rheumatology Unit, AP-HP, Necker-Enfants Malades Hospital, Paris, France;

5. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY;

6. Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan;

7. Institute of Environmental Medicine, UNIKA-T, Technical University and Helmholtz Center Munich, Augsburg, Germany;

8. Christine Kühne–Center for Allergy Research and Education (CK-CARE), Davos, Switzerland;

9. Immunology and Reumatholoy Department, Juan Pedro Garrahan National Hospital of Pediatrics, Buenos Aires, Argentina;

10. Department of Preclinics, School of Medicine, Valparaíso University and Department of Pediatrics, Padre Hurtado-Clinica Alemana de Santiago Hospital, Valparaíso, Chile;

11. Allergy and Immunology Division, Edgardo Rebagliati Martins National Hospital, Lima, Peru;

12. Pediatric Hematology-Oncology Unit, AP-HP, Robert Debré Hospital, Paris, France;

13. Pediatric Oncology and Hematology Unit, Children Hospital, Vandoeuvre-les-Nancy, France;

14. Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India;

15. Meyer Children's Hospital, Haifa, Israel;

16. Department of Pediatric Immunology, Hematology and Infectious Diseases, Utrecht University Medical Center, Utrecht, The Netherlands;

17. Department of Pediatrics, Infectious Disease, Clinical Immunology and Allergy Division, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey;

18. Division of Pediatric Pulmonology, Allergy, Immunology, and Sleep Medicine, Rainbow Babies and Children's Hospital, Case Medical Center, Cleveland, OH;

19. Dr. von Hauner Children’s Hospital, Ludwig Maximilian University, Munich, Germany;

20. Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Ibn Rochd Hospital, King Hassan II University, Casablanca, Morocco;

21. Department of Immunology, Son Espases University Hospital, Palma de Mallorca, Spain;

22. Department of Pediatrics, Leuven University Hospitals, Leuven, Belgium;

23. Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia;

24. Division of Immunology, University Children’s Hospital and Children’s Research Centre, University of Zurich, Zurich, Switzerland;

25. Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;

26. Center for Chronic Immunodeficiency, Freiburg University Medical Center and University of Freiburg, Freiburg, Germany;

27. Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases, Nijmegen, The Netherlands;

28. Study Center for Immunodeficiencies, Necker-Enfants Malades Hospital, AP-HP, Paris, France;

29. Department of Infectious Diseases and Pediatric Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;

30. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan;

31. Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom;

32. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;

33. Howard Hughes Medical Institute, New York, NY; and

34. Department of Infectious and Tropical Diseases, Necker-Enfants Malades Hospital, AP-HP, Paris, France

Abstract

Key Points AD STAT1 GOF is the most common genetic cause of inherited CMC and is not restricted to a specific age or ethnic group. STAT1 GOF underlies a variety of infectious and autoimmune features, as well as carcinomas and aneurysms associated with a poor outcome.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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