Lipoproteins: familial defective apoB-100: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Lipoproteins: familial defective apoB-100

Sample item

A 32-year-old man has LDL cholesterol 300 mg/dL and tendon xanthomas, as did his father. LDL receptor expression on his cells is normal and the LDLR and PCSK9 genes are normal, but his LDL binds receptors poorly. What is the most likely defect?

AMutation in the receptor-binding domain of apolipoprotein B-100BAbsence of LDL receptors on the cell surfaceCDeficiency of lipoprotein lipaseDGain-of-function mutation in PCSK9

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

A. Mutation in the receptor-binding domain of apolipoprotein B-100

Apolipoprotein B-100 on LDL is the ligand for the LDL receptor. A substitution such as Arg3500Gln impairs binding, so LDL is cleared slowly and accumulates, giving a familial hypercholesterolaemia phenotype with a normal receptor. It is called familial defective apoB-100.

Option by option

A. Mutation in the receptor-binding domain of apolipoprotein B-100 (correct)
Correct. The receptor is normal, but the ligand binds it poorly.
B. Absence of LDL receptors on the cell surface
Absent receptors are excluded by normal receptor expression and LDLR sequence.
C. Deficiency of lipoprotein lipase
Lipoprotein lipase deficiency raises triglycerides and chylomicrons, not isolated LDL.
D. Gain-of-function mutation in PCSK9
PCSK9 gain of function is excluded by normal PCSK9 sequencing.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is A, Mutation in the receptor-binding domain of apolipoprotein B-100. Apolipoprotein B-100 on LDL is the ligand for the LDL receptor.

Why is "Absence of LDL receptors on the cell surface" not the answer?

Absent receptors are excluded by normal receptor expression and LDLR sequence.

Why is "Deficiency of lipoprotein lipase" not the answer?

Lipoprotein lipase deficiency raises triglycerides and chylomicrons, not isolated LDL.

Why is "Gain-of-function mutation in PCSK9" not the answer?

PCSK9 gain of function is excluded by normal PCSK9 sequencing.

What concept does this question test?

It tests Lipoproteins: familial defective apoB-100 in Biochemistry. A substitution such as Arg3500Gln impairs binding, so LDL is cleared slowly and accumulates, giving a familial hypercholesterolaemia phenotype with a normal receptor. It is called familial defective apoB-100.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Lipoproteins: familial defective apoB-100?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.