Familial hypercholesterolaemia (FH) is caused by LDL receptor mutations. Which LDL receptor mutation class would result in receptor synthesis but failure to transport to cell surface?

• A Class 1 mutation: null allele, no receptor protein synthesised
• B Class 3 mutation: binding-defective, receptor on cell surface but fails to bind LDL
• C Class 2 mutation: transport-defective, receptor synthesised in ER but cannot traffic to Golgi/cell surface ✓
• D Class 4 mutation: internalisation-defective, receptor binds LDL but cannot cluster in clathrin-coated pits

Explanation

LDL receptor mutations are classified into 5 classes based on their functional defect: Class 1 (null) — no receptor synthesis; Class 2 (transport-defective) — receptor is synthesised but fails to traffic from ER to Golgi, remaining stuck in ER; Class 3 (binding-defective) — receptor reaches cell surface but has reduced or absent LDL binding due to ligand-binding domain mutations; Class 4 (internalisation-defective) — receptor binds LDL but cannot cluster in clathrin-coated pits due to NPXY motif mutations in cytoplasmic tail; Class 5 (recycling-defective) — receptor cannot recycle to cell surface after endosomal dissociation. The question specifically asks about synthesis-but-no-surface-expression, which is Class 2.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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