Medical genetics: trinucleotide repeat disorders: practice question

A Anatomy 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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Anatomy · Medical genetics: trinucleotide repeat disorders

Sample item

A boy develops chorea and cognitive decline at age 12. His father developed similar symptoms at age 45, and the boy has 70 CAG repeats in HTT whereas his father has 45. Which mechanism best explains the earlier onset?

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

The answer and the reasoning

D. Further CAG expansion during spermatogenesis, producing anticipation

Huntington disease is an autosomal dominant trinucleotide repeat disorder in which longer CAG repeats cause earlier onset. The repeat tends to expand further when transmitted by the father because of instability in spermatogenesis, so juvenile onset is usually paternal. Fragile X, by contrast, expands from a premutation through oogenesis.

Option by option

  • A. Mitochondrial heteroplasmy

    Huntington disease is nuclear, not mitochondrial, so heteroplasmy does not apply.

  • B. Uniparental disomy of chromosome 4

    Uniparental disomy does not explain anticipation in a dominantly inherited expansion disorder.

  • C. Genomic imprinting of the maternal allele

    Imprinting does not explain a progressive increase in repeat number across generations.

  • D. Further CAG expansion during spermatogenesis, producing anticipation (correct)

    Correct. Paternal transmission favours expansion and anticipation in Huntington disease.

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 Anatomy question

What is the answer to this Anatomy question?

The best answer is D, Further CAG expansion during spermatogenesis, producing anticipation. Huntington disease is an autosomal dominant trinucleotide repeat disorder in which longer CAG repeats cause earlier onset.

Why is "Mitochondrial heteroplasmy" not the answer?

Huntington disease is nuclear, not mitochondrial, so heteroplasmy does not apply.

Why is "Uniparental disomy of chromosome 4" not the answer?

Uniparental disomy does not explain anticipation in a dominantly inherited expansion disorder.

Why is "Genomic imprinting of the maternal allele" not the answer?

Imprinting does not explain a progressive increase in repeat number across generations.

What concept does this question test?

It tests Medical genetics: trinucleotide repeat disorders in Anatomy. The repeat tends to expand further when transmitted by the father because of instability in spermatogenesis, so juvenile onset is usually paternal. Fragile X, by contrast, expands from a premutation through oogenesis.

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 Medical genetics: trinucleotide repeat disorders?

Learn every nerve by its route, its muscles and what a lesion looks like at the bedside. That one habit answers a large share of questions. Then use the flashcards and the other Anatomy 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.