A novel STAT3 splice-site variant in a kindred with autosomal dominant hyper IgE syndrome
Abstract
Background: Dominant negative STAT3 loss-of-function is the most common genetic cause of hyper-IgE syndrome (HIES). Patients may present with a host of both immune and non-immune manifestations, including connective tissue abnormalities, recurrent infections, malignant predisposition, and biochemical evidence of elevated serum IgE or eosinophilia.
Aim: To describe a novel splice-site variant in STAT3 resulting in HIES.
Methods: Case report of two family members with HIES.
Results: A proband and his son presented with neonatal-onset pustular rash, recurrent skin and sinopulmonary infections and elevated serum IgE and were diagnosed with AD-HIES. They were identified to harbor a novel splice-site variant in the DNA-binding domain (DBD) of STAT3: c.1110-3C>G, predicted to result in defective splicing in exon 12. Interestingly, a number of other patients with AD-HIES have mutations affecting the same splice-site, suggesting this may be a hot-spot for mutagenesis.
Conclusion: Splice-site mutations in the DBD of STAT3 are increasingly identified as a cause of AD-HIES. Future work is required to delineate whether patients with splice-site mutations have unique clinical characteristics, supporting efforts for genotype-phenotype correlation in this disease.
Statement of Novelty: We present a novel splice-site mutation in the DNA-binding domain of STAT3 leading to autosomal dominant hyper-IgE syndrome.
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LymphoSign Journal
Volume 10 • Number 1 • March 2023
Pages: 15 - 19
History
Received: 27 February 2023
Accepted: 17 March 2023
Accepted manuscript online: 17 March 2023
Version of record online: 18 April 2023
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© 2023.
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OriScott, MarinaSham, LauraAbrego Fuentes, MyraPereira, DanieleMerico, and Vy HDKim. 2023. A novel STAT3 splice-site variant in a kindred with autosomal dominant hyper IgE syndrome. LymphoSign Journal.
10(1): 15-19. https://doi.org/10.14785/lymphosign-2023-0002
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