A 32-year-old man presents with episodic hemolytic anemia, dark morning urine, and thrombosis. Flow cytometry shows a deficiency of CD55 and CD59 on red blood cells. The somatic mutation responsible for this disorder occurs in which gene?

• A Complement factor H gene on chromosome 1
• B PIGA gene on the X chromosome ✓
• C DAF gene encoding CD55 directly
• D PIGB gene encoding dolichol phosphate mannose synthase

Explanation

Paroxysmal nocturnal hemoglobinuria (PNH) results from a somatic mutation in the PIGA gene (phosphatidylinositol glycan class A), located on the X chromosome. PIGA encodes an enzyme essential for the first step of GPI anchor biosynthesis; loss of GPI anchors leads to deficiency of all GPI-linked proteins including CD55 (DAF) and CD59 (protectin), which normally protect erythrocytes from complement-mediated lysis. The mutation is in hematopoietic stem cells, not directly in CD55 or complement factor H 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.