STAT3 in-frame triplet deletion in an Italian patient affected by Job’s disease for over 25 years

OBJECTIVE: To investigate STAT3 involvement in the pathogenesis of Job’s disease (Hyper-IgE syndrome, HIES; OMIM 147060) in an Italian patient with a long history of recurrent infections. SUBJECT AND METHODS: DNA was isolated from a woman with high serum IgE levels (900 kU/L) and suffering for over 25 years from recurrent eczematoid dermatitis of the face, neck, buttocks, and knees, pustular dermatitis, abscesses all over her body, and chronic mucocutaneous candidiasis. All STAT3 exons and exon-introns were PCR amplified and sequenced. RESULTS: An in-frame deletion of the triplet coding for Val463 was identified. The missing amino acid lies in the DNA-binding domain of STAT3 that binds to the IL-6 responsive element. CONCLUSIONS: Val463 deletions of independent origin have been identified in familial and sporadic HIES patients from different populations. Our results further support the hypothesis of a mutational hot spot in STAT3 exon 16 linked to Job’s syndrome. CLINICAL RELEVANCE: Molecular-genetic investigations on Italian HIES patients are at their very beginning and our results suggest that STAT3 mutations should be searched for in subjects presenting with persisting elevated IgE levels, eczema, staphylococcal abscesses and other recurrent infections.