Journal of Clinical Immunology

, Volume 38, Issue 7, pp 753–756 | Cite as

Novel STAT1 Gain-of-Function Mutation Presenting as Combined Immunodeficiency

  • Stella P. Hartono
  • Alexander Vargas-Hernández
  • Mark J. Ponsford
  • Ivan K. Chinn
  • Stephen Jolles
  • Keith Wilson
  • Lisa R. ForbesEmail author
Letter to Editor

To the Editor:

Heterozygous STAT1 gain-of-function (GOF) mutation represents a broad spectrum of clinical presentations beyond chronic mucocutaneous candidiasis (CMC), encompassing not only fungal, but also bacterial, viral infections and autoimmune manifestations. Most STAT1 GOF mutations are located in the coiled-coil (CCD) and DNA-binding domains (DBD) [1] resulting in hyper-phosphorylation of STAT1, thereby enhancing target gene expression. Here, we present a patient with a de novo novel heterozygous STAT1 GOF mutation that presented with a complex clinical phenotype with progressive combined immunodeficiency (CID) without classical fungal infections or autoimmune features. This case highlights a phenotypic disease expansion alongside presentation of a novel STAT1 GOF mutation and emphasizes the importance of whole exome sequencing (WES) in diagnosis of primary immunodeficiency diseases.

A 23-year-old Caucasian female presented with recurrent sinusitis, otitis, respiratory...


STAT1 gain of function Chronic mucocutaneous candidiasis Combined immunodeficiency Common variable immunodeficiency Hematopoietic stem cell transplant 



Signal transducer and activator of transcription 1




Chronic mucocutaneous candidiasis


Coiled-coil DNA


DNA-binding domain


Combined immunodeficiency


Whole exome sequencing


High resolution computed tomography


Common variable immunodeficiency


Immunoglobulin replacement therapy


Natural killer


Hematopoietic stem cell transplant


Graft versus host disease



The authors would like to thank Drs. James R. Lupski, Richard A. Gibbs, and Zeynep H. Coban Akdemir for whole exome sequencing and bioinformatics support. We greatly appreciate the support of Dr. Jordan Orange and the Texas Children’s Hospital Jeffrey Modell Diagnostic and Research Center. We also appreciate the help of Ms. Tram N. Cao and Ms. Anaid G. Reyes for research coordination.

Funding Sources

This study received financial support from the Chao Physician Scientist Junior Faculty Award, Jeffrey Modell Foundation Diagnostic and Research Center for Primary Immunodeficiencies, and NIH-NHGRI/NHLBI award UM1HG006542 (Baylor-Hopkins Center for Mendelian Genomics).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest

Supplementary material

10875_2018_554_MOESM1_ESM.pdf (3.7 mb)
ESM 1 (PDF 3771 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Stella P. Hartono
    • 1
  • Alexander Vargas-Hernández
    • 1
    • 2
  • Mark J. Ponsford
    • 3
  • Ivan K. Chinn
    • 1
    • 2
  • Stephen Jolles
    • 3
  • Keith Wilson
    • 4
  • Lisa R. Forbes
    • 1
    • 2
    Email author
  1. 1.Department of PediatricsBaylor College of MedicineHoustonUSA
  2. 2.Center for Human Immunobiology, Immunology, Allergy, Rheumatology, and RetrovirologyTexas Children’s HospitalHoustonUSA
  3. 3.Immunodeficiency Centre for Wales, Department of ImmunologyUniversity Hospital of WalesCardiffUK
  4. 4.Department of HaematologyUniversity Hospital of WalesCardiffUK

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