In paroxysmal nocturnal hemoglobinuria (PNH), the absence of GPI-anchored proteins is due to somatic mutation in which gene in hematopoietic stem cells?

• A C3 (complement component 3)
• B PIGA (phosphatidylinositol glycan anchor biosynthesis class A) ✓
• C CD59 gene directly
• D PIGB (a downstream enzyme in GPI synthesis)

Explanation

PNH is caused by somatic mutation in PIGA, an X-linked gene encoding an enzyme essential for the first step of GPI-anchor biosynthesis (addition of GlcNAc to phosphatidylinositol). Because PIGA is X-linked and a single somatic mutation inactivates the functional copy, the affected clone cannot synthesize any GPI anchors. This results in global absence of GPI-anchored proteins on the cell surface, including CD55 (decay-accelerating factor) and CD59 (protectin) — both of which normally inhibit complement. Without CD55 and CD59, RBCs (and other cells) are exquisitely sensitive to complement-mediated lysis. Mutations in CD59 alone would not account for all GPI protein deficiency; PIGB mutations cause a very rare congenital disorder.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.