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Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis
Oded Breuer1, Hagit Daum2, Malena Cohen-Cymberknoh1
1Department of Pediatrics and Pediatric Pulmonary Unit, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
Respiratory Medicine
|April 22, 2017
Summary
A genetic mutation in STAT1 was identified as a cause of severe non-cystic fibrosis bronchiectasis. This STAT1 gain-of-function mutation impairs memory B cells, leading to lung disease.
Area of Science:
- Genetics
- Immunology
- Pulmonology
Background:
- Many patients with non-cystic fibrosis (CF) bronchiectasis lack a clear cause.
- Immunodeficiency syndromes are implicated, but the precise mechanisms remain unclear.
Observation:
- A patient with severe non-CF bronchiectasis underwent whole exome sequencing (WES) and immunophenotyping.
- Genetic analysis revealed an autosomal dominant gain-of-function (AD-GOF) mutation in STAT1.
Findings:
- The patient exhibited increased STAT1 phosphorylation upon interferon-gamma stimulation.
- Reduced class-switched memory B cells were observed, alongside minor CD8 T cell alterations.
Implications:
- Early WES is beneficial for diagnosing non-CF bronchiectasis.
- STAT1 AD-GOF mutations and impaired memory B cells may predispose individuals to suppurative sinopulmonary disease.
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