A 2-year-old girl is brought with recurrent pneumonias, eczematous rash, thrombocytopenia with small platelets on blood film, and elevated IgA and IgE but markedly low IgM. She has a maternal uncle who died in childhood with similar symptoms. Which gene is most likely mutated?
- A RAG1/RAG2
- B WAS (WASP gene) ✓
- C BTK
- D STAT3
Explanation
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder caused by mutations in the WASP (Wiskott-Aldrich Syndrome Protein) gene, encoding a protein critical for actin polymerization in hematopoietic cells. The classic triad is: (1) eczema, (2) thrombocytopenia with small-sized platelets (microplatelets), and (3) immunodeficiency characterized by low IgM, elevated IgA and IgE, and variable IgG. Recurrent infections (encapsulated bacteria, viruses, fungi) occur. X-linked inheritance explains the maternal uncle's death. RAG1/RAG2 mutations cause SCID (absent T and B cells). BTK mutations cause X-linked agammaglobulinemia (absent B cells, all immunoglobulins low). STAT3 mutations cause Hyper-IgE syndrome (Job syndrome), which has elevated IgE, eczema, and recurrent staphylococcal abscesses but normal platelet size.
Reference: Ghai Essential Pediatrics, 10th ed.
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