STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti–IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Expression Analysis of MiR-21, MiR-205, and MiR-342 in Breast Cancer in Iran MiR-21;MiR-205;MiR-342;P53;breast cancer;sybr green I real time RT-P.C.R.; MicroRNAs (miRNAs) are short non-coding RNA molecules characterized by their regulatory roles in cancer and gene expression. We analyzed the expression of miR-21, miR-205, and miR-342 in 59 patients with breast cancer. Samples were divided into three different groups according to their immunohistochemistry (IHC) classification: ER- positive and/or PR-positive group ($ER^+$ and/or $PR^+$; group I); HER2-positive group ($HER^{2+}$; group II); and ER/ PR/ HER2- negative ($ER^-$/ $PR^-$/ $HER^{2-}$; group III) as the triple negative group. The expression levels of the 3 miRNAs were analyzed in the tumor samples and the compared with the normal neighboring dissected tumor (NNDT) samples in all three groups. The expression of miR-21 was similar in all three groups. In patients positive for P53 by IHC, positive for axillary lymph node metastasis and higher tumor stages, it appeared to have significantly elevated. However, significant increase was not found among the 18 fibroadenoma samples. Both miR-205 and miR-342 expressions were significantly down regulated in group III. We conclude that miR-21 does not discriminate between different breast cancer groups. In contrast, miR-205 and miR-342 may be used as potential biomarkers for diagnosis of triple negative breast cancer.

Objectives: Antioxidant treatment with Iron chelating agents is one of the suggested treatments for fatty liver disease, which has become an important health problem in the recent decades. In this study the authors evaluated the general antioxidant, iron chelating, and sugar and fat absorption characteristics of green tea. Methods: Patients with non-alcoholic fatty liver disease were randomly assigned to 2 groups for a double blind clinical trial. Patients in the intervention group received 550 milligrams of green tea tablets daily as well as nutritional education for 3 months. The control group received the same protocol with green tea replaced with placebo tablets. Results: After 3 months, 45 participants (21 in the intervention and 24 in the placebo group) completed the follow-up. The change in body mass index (BMI), aspartate aminotransferase (AST), and fasting blood sugar (FBS) was significantly different between the 2 groups, while the change in total iron binding capacity (TIBC), ferritin, alanine transaminase (ALT), HOMA, and weight did not show a significant difference. Conclusions: The difference between the 2 groups was mainly observed in anthropometrics, liver enzyme, and metabolic indicators, although the difference might not have been highlighted due to the effectiveness of routine treatments, that both groups received. Keywords: Green Tea; NAFLD; Iron

Key Clinical Message: MED23 deficiency causes the autosomal recessive Intellectual Disability (ID). Here we report an Iranian case with nonsyndromic ID presenting with developmental delay, microcephaly, hypotonia, severe ID, speech delay, and spasticity, who was homozygous for the novel MED23 c.670C>G variant. These results expand the clinical and mutation spectrum of MED23 deficiency.