Whole-exome sequencing analysis using her peripheral blood revealed a heterozygous mutation in the STAT3 gene, which is related to autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES).
Job syndrome or autosomal dominant hyper IgE syndrome because of heterozygous loss-of-function mutations with dominant negative effect in signal transducer and activator of transcription-3 is the prototype of these disorders.
Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES).
This article focuses on loss of function STAT3 mutations causing autosomal-dominant hyper-IgE syndrome and dedicator of cytokinesis 8 deficiency, with discussion of other more recently described diseases.
Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively.
Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease.
STAT3-deficient hyper-IgE syndrome is characterized by elevated serum IgE levels, recurrent infections and eczema, and characteristic skeletal anomalies.
The majority of autosomal dominant HIES (AD HIGE) is due to hypomorphic mutations in the signal transducer and the activator of transcription 3 (STAT3) gene.
This study was undertaken to functionally characterize neutrophils in STAT3-deficient HIES patients and to analyze whether the patients` eosinophilia affects the neutrophil phenotype in S. aureus infection.
Patients with defects in the Th17/IL-17 axis, such as patients harboring loss-of-function STAT3 mutations (autosomal-dominant hyper IgE syndrome; AD-HIES) present with recurrent oral fungal infections.
Loss-of-function mutations in the signal transducer and activator of transcription 3 gene (<i>stat3</i>) result in autosomal dominant hyper-IgE syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including frequent pneumococcal and staphylococcal pneumonias.
The complete loss of STAT3 is not compatible with life and even partial loss of function mutations lead to debilitating pathologies like hyper IgE syndrome.
Regulation of OPN gene through IL-6-mediated STAT3 activation and its significant dysregulation in STAT3 LOF HIES subjects could make OPN a plausible candidate involved in the pathogenesis of dental/facial manifestations in HIES.
Studies of HIES have been further complicated by the lack of a high serum IgE phenotype in all mouse models of the disease other than two Stat3 mutant strains.
Both autosomal dominant (AD) HIES due to STAT3 mutations and autosomal recessive (AR) HIES due to PGM3, SPINK5, DOCK8 and TKY2 mutations have been reported.
STAT2 deficiency has been described in 5 family members and is characterized by selective susceptibility to viral infections, whereas STAT3 loss-of-function (LOF) mutations are causative of the autosomal-dominant hyper-IgE syndrome (HIES), a condition that is characterized by cutaneous and respiratory infections in association with mucocutaneous candidiasis, eczema, skeletal and connective tissue abnormalities, eosinophilia, and high levels IgE.
STAT 3 deficiency (autosomal dominant hyper immunoglobulin E syndrome (AD-HIES)) is a primary immunodeficiency disorder with multi-organ involvement caused by dominant negative signal transducer and activator of transcription gene 3 (STAT3) mutations.
Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome.