Paroxysmal nocturnal hemoglobinuria (PNH) results from a somatic mutation in which gene, causing deficiency of which anchoring protein?

• A ANKRD26 gene; ankyrin protein
• B PIEZO1 gene; mechanosensitive ion channel
• C PIGA gene; GPI (glycosylphosphatidylinositol) anchor ✓
• D CR1 gene; complement receptor 1

Explanation

PNH results from an acquired somatic mutation in the PIGA gene in hematopoietic stem cells, which encodes an enzyme required for synthesis of the GPI (glycosylphosphatidylinositol) anchor. Loss of GPI anchoring means complement regulatory proteins CD55 (DAF) and CD59 (MIRL) are absent from the cell surface, leaving RBCs, platelets, and granulocytes vulnerable to complement-mediated destruction. CD59 deficiency is the primary culprit for hemolysis. Flow cytometry using FLAER (aerolysin) is the gold-standard diagnostic test.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.