A 12-year-old boy has recurrent cold staphylococcal abscesses, pneumonia with pneumatoceles, coarse facies, retained primary teeth, and eczema. Serum IgE is 9500 IU/mL. Which molecular defect is most likely?
- A Loss-of-function mutation in CYBB
- B Dominant-negative mutation in STAT3 ✓
- C Mutation in the WAS gene
- D Deficiency of CD40 ligand
Correct answer: B. Dominant-negative mutation in STAT3
Explanation
Autosomal dominant hyper-IgE (Job) syndrome is caused by dominant-negative STAT3 mutations impairing Th17 differentiation, which explains susceptibility to extracellular bacteria and Candida through defective IL-17 mediated neutrophil recruitment. The clinical constellation includes cold abscesses, pneumatoceles, coarse facies, and retained deciduous teeth. CYBB defects cause chronic granulomatous disease, which does not feature elevated IgE or skeletal findings.
Reference: Nelson Textbook of Pediatrics, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.