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Updated: Nov 19, 2025

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
Published on: October 9, 2016
Clinical and Immunological Heterogeneity in Japanese Patients with Gain-of-Function Variants in STAT3
Kay Tanita1, Fumiaki Sakura2, Ryusuke Nambu3,4,5
1Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Purpose:
Germline loss-of-function variants in the signal transducer and activator of transcription 3 (STAT3) gene result in autosomal dominant hyper IgE syndrome, whereas somatic gain-of-function (GOF) variants in STAT3 are associated with some malignancies. In addition, germline GOF variants in STAT3 are linked to disorders involving autoimmunity and lymphoproliferation. In this study, we describe five Japanese families with germline GOF variants in STAT3, including three novel variants. We also present the clinical and immunological characteristics of these patients.
Methods:
Eight patients from five families were enrolled in this study. We performed genetic and immunological analyses, and collected the associated clinical information.
Results:
We identified five heterozygous variants in STAT3 using whole-exome sequencing and target gene sequencing. Two of these (E286G and T716M) were previously reported and three (K348E, E415G, and G618A) were novel. A STAT3 reporter assay revealed that all of the variants were GOF. However, the immunological and clinical characteristics among the patients were highly variable.
Conclusion:
Patients with STAT3 GOF variants exhibited clinical and immunological heterogeneity with incomplete penetrance.
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