Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT). Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis.
This is the first time such mutations are reported and these variants are predicted to be damaging. Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. NGS was performed, and the results were confirmed by Sanger sequencing. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications.
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