Novel germline STAT3 gain-of-function mutation causes autoimmune diseases and severe growth failure.

Background

In recent years, germline gain-of-function (GOF) mutations in signal transducer and activator of transcription 3 (

Objective

We sought to assess whether a novel

Methods

A pediatric patient with idiopathic pulmonary hemosiderosis, autoimmune thyroiditis, inflammatory bowel disease unclassified, leukocytosis, thrombocytosis, and severe growth failure was examined.

Results

This 7-year-old boy had idiopathic pulmonary hemosiderosis at the age of 6 months. Despite high-dose steroid therapy, pulmonary fibrosis progressed. Furthermore, he presented with severe growth failure, autoimmune thyroiditis, leukocytosis, thrombocytosis, and inflammation bowel disease unclassified. Given the presence of multiple autoimmune diseases, whole-exome sequencing was performed, which detected germline

Conclusions

Tocilizumab may be effective for patients with STAT3 GOF mutation, including those requiring long-term management of idiopathic pulmonary hemosiderosis. Diagnosis of patients with early-onset multiorgan autoimmune diseases in which STAT3 GOF is suspected should be confirmed by genetic testing and functional analysis to consider the introduction of targeted therapies.

Informations de copyright

© 2024 The Author(s).

Déclaration de conflit d'intérêts

This work was supported by the Initiative on Rare and Undiagnosed Diseases (grant no. JP23ek0109549) from the 10.13039/100009619Japan Agency for Medical Research and Development. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.