Molecular and Phenotypic Characterization of Nine Patients with STAT1 GOF Mutations in China

  • Xuemei Chen
  • Qiling Xu
  • Xiaolin Li
  • Linlin Wang
  • Lu Yang
  • Zhi Chen
  • Ting Zeng
  • Xiuhong Xue
  • Tao Xu
  • Yanping Wang
  • Yanjun Jia
  • Qin Zhao
  • Junfeng Wu
  • Fangfang Liang
  • Xuemei Tang
  • Jun Yang
  • Yunfei AnEmail author
  • Xiaodong ZhaoEmail author
Original Article



Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes.


We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations.


This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression.


Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.


STAT1 gain-of-function innate immunity adaptive immunity 



We thank the patients and their families for their kind cooperation in this study. We thank the members of the laboratory for technical assistance. We thank the doctors and nurses for supporting this project. We also thank Satoshi Okada for technical assistance.

Authors’ Contributions

XM.C., YF.A., and XD.Z. designed the study and wrote the manuscript; XM.C., L.Y., Z.C., T.Z., XH.X., T.X., YP.W., YJ.J., Q.Z., and JF.W. did the experiments and analyzed patients’ data; XM.C., QL.X., XL.L, LL.W., FF.L, J.Y, XM.T., and YF.A. followed the patients; all authors reviewed the manuscript before publication.

Funding Information

This work was supported by the Public Welfare Scientific Research Project of China (201402012).

Compliance with Ethical Standards

Informed consent was obtained from all individual participants included in the study. This study was conducted in accordance with the tenets of the Declaration of Helsinki and was approved by the ethics committee of Chongqing Medical University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Xuemei Chen
    • 1
    • 2
  • Qiling Xu
    • 1
    • 2
  • Xiaolin Li
    • 3
  • Linlin Wang
    • 4
  • Lu Yang
    • 1
    • 2
  • Zhi Chen
    • 1
    • 2
  • Ting Zeng
    • 1
    • 2
  • Xiuhong Xue
    • 1
    • 2
  • Tao Xu
    • 1
    • 2
  • Yanping Wang
    • 1
    • 2
  • Yanjun Jia
    • 1
    • 2
  • Qin Zhao
    • 1
    • 2
  • Junfeng Wu
    • 5
  • Fangfang Liang
    • 1
    • 2
  • Xuemei Tang
    • 5
  • Jun Yang
    • 4
  • Yunfei An
    • 1
    • 2
    • 5
    Email author
  • Xiaodong Zhao
    • 1
    • 2
    • 5
    Email author
  1. 1.Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders (Chongqing)China International Science and Technology Cooperation base of Child development and Critical Disorders; Children’s Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Chongqing Key Laboratory of Child Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityChongqingChina
  3. 3.Department of Pediatric Rheumatology and ImmunologyZhongshan Boai Hospital Affiliated Southern Medical UniversityZhongshanChina
  4. 4.Department of Rheumatology and ImmunologyShenzhen Children’s HospitalShenzhenChina
  5. 5.Department of Rheumatology and ImmunologyChildren’s Hospital of Chongqing Medical UniversityChongqingChina

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