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Signal-transducer-and-activator-of-transcription-3 (STAT3) is a central regulator of immune homeostasis. STAT3 levels are strictly controlled and STAT3 impairment contributes to several diseases including the monogenic autosomal-dominant hyper-IgE syndrome (AD-HIES). We investigated patients of four consanguineous families with an autosomal-recessive disorder resembling the phenotype of AD-HIES, with symptoms of immunodeficiency, recurrent infections, skeletal abnormalities, and elevated IgE. Patients presented with reduced STAT3 expression and diminished Th17 cell numbers, in absence of STAT3 mutations. We identified homozygous nonsense mutations in ZNF341, encoding a zinc-finger transcription factor. Wild-type ZNF341 bound to and activated the STAT3 promoter, whereas the mutant variants showed impaired transcriptional activation, partly due to nuclear translocation failure. In summary, nonsense mutations in ZNF341 account for the STAT3-like phenotype in four autosomal-recessive kindreds. Thus, ZNF341 is a previously unrecognized regulator of immune homeostasis.

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Background Chronic spontaneous urticaria is well‐described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods This retrospective study followed children up to 18 years old, diagnosed with chronic spontaneous urticaria, between the years 2002‐2018, and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments, and outcomes were extracted from electronic medical records. Results Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, and 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25 ± 15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty‐seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2%, and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance Chronic spontaneous urticaria in children is a self‐limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population, increasing the possibility of a special subgroup of TH2‐related chronic urticaria in children.

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