A 30-year-old woman has hemolytic anemia with episodic dark urine after infections. Flow cytometry of red cells shows absence of CD55 and CD59. The underlying defect is a somatic mutation in which gene?
- A DAF (CD55) gene directly
- B HMOX1
- C PIGA ✓
- D CD59 gene directly
Explanation
Paroxysmal nocturnal hemoglobinuria (PNH) is caused by a somatic mutation in the PIGA gene (phosphatidylinositol glycan class A) in a hematopoietic stem cell. PIGA encodes an enzyme essential for the first step in GPI (glycosylphosphatidylinositol) anchor biosynthesis. Without a functional GPI anchor, multiple complement regulatory proteins including CD55 (decay accelerating factor) and CD59 (protectin/MAC-inhibitory protein) cannot be attached to the cell surface. The resulting complement-mediated intravascular hemolysis explains the hemoglobinuria. The mutation is in PIGA, not in the individual protein genes.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.