Novel and recurrent STAT3 mutations in hyper-IgE syndrome patients from different ethnic groups.

摘要: We performed clinical, immunological and genetic studies of 12 hyper-IgE syndrome (HIES) patients from 4 Hungarian, 2 Lebanese, one Russian, Polish, Swedish families with autosomal dominant (AD) or sporadic forms the disease to reveal cross-ethnicity recurrent novel mutations in signal transducer activator transcription-3 gene (STAT3). Four 3 Hungarian families, patient carried heterozygous R382W germline mutation at DNA-binding site STAT3. The V637M affecting SRC homology (SH2) domain was detected Lebanese Polish family, V463del deletion located unveiled another family. A H332Y STAT3 three a Gypsy family also found. segregation this HIES, restriction fragment length polymorphism analysis controls negligible production upon IL-6 stimulation monocyte chemotactic protein-1 by patient's blood mononuclear cells suggested that disease-causing. These data suggest, negative SH2 domains cause AD cases HIES different ethnic groups as predominant found 5 9 families. Functional support may result loss function leads phenotype.