A 12-year-old boy has recurrent cold staphylococcal abscesses, pneumatoceles following pneumonia, coarse facies, retained primary teeth, and eczematous rash. Serum IgE is markedly elevated at 8000 IU/mL. Mutations in which gene are responsible?

• A WAS gene encoding Wiskott-Aldrich syndrome protein
• B CYBB gene encoding gp91phox
• C DOCK8 gene
• D STAT3 gene ✓

Explanation

Hyper-IgE (Job) syndrome is caused by autosomal dominant mutations in STAT3, which impair Th17 cell differentiation. Defective Th17 responses reduce IL-17 mediated neutrophil recruitment to skin and lung, explaining cold abscesses and recurrent Staphylococcus aureus pneumonia with pneumatoceles. The WAS mutation causes eczema with thrombocytopenia and small platelets, CYBB causes chronic granulomatous disease, and DOCK8 causes a recessive combined immunodeficiency with viral susceptibility rather than the classic triad described here.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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