Trinucleotide repeats: Huntington disease and anticipation: 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 · Trinucleotide repeats: Huntington disease and anticipation

Sample item

A 30-year-old man develops chorea, irritability and cognitive decline. His father developed similar symptoms at 52. Genetic testing shows a larger CAG expansion in the man than in his father. Which statement best explains his earlier onset?

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

The answer and the reasoning

C. The CAG repeat in HTT expands further during spermatogenesis, so paternal transmission shows anticipation

Huntington disease is an autosomal dominant polyglutamine disorder from CAG repeat expansion in the HTT gene on chromosome 4. Longer repeats give earlier onset, and the repeat is especially unstable in male germ cells, so anticipation is most marked with paternal inheritance. This contrasts with fragile X, where large expansions are generated mainly in maternal meiosis.

Option by option

  • A. The father's normal allele was lost through uniparental disomy

    Uniparental disomy is the mechanism in some imprinting disorders and not in Huntington disease.

  • B. The son inherited a deletion of chromosome 4

    The disorder results from a repeat expansion and not from a chromosome deletion.

  • C. The CAG repeat in HTT expands further during spermatogenesis, so paternal transmission shows anticipation (correct)

    Repeat instability in the male germ line gives anticipation.

  • D. A new point mutation in the mitochondrial genome arose in the son

    The disease is caused by a nuclear gene repeat, not by a mitochondrial point mutation.

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.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is C, The CAG repeat in HTT expands further during spermatogenesis, so paternal transmission shows anticipation. Huntington disease is an autosomal dominant polyglutamine disorder from CAG repeat expansion in the HTT gene on chromosome 4.

Why is "The father's normal allele was lost through uniparental disomy" not the answer?

Uniparental disomy is the mechanism in some imprinting disorders and not in Huntington disease.

Why is "The son inherited a deletion of chromosome 4" not the answer?

The disorder results from a repeat expansion and not from a chromosome deletion.

Why is "A new point mutation in the mitochondrial genome arose in the son" not the answer?

The disease is caused by a nuclear gene repeat, not by a mitochondrial point mutation.

What concept does this question test?

It tests Trinucleotide repeats: Huntington disease and anticipation in Biochemistry. Longer repeats give earlier onset, and the repeat is especially unstable in male germ cells, so anticipation is most marked with paternal inheritance. This contrasts with fragile X, where large expansions are generated mainly in maternal meiosis.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. 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 Trinucleotide repeats: Huntington disease and anticipation?

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.