Medical genetics: germline mosaicism: 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: germline mosaicism

Sample item

Two healthy parents have had two children with severe autosomal dominant osteogenesis imperfecta. Neither parent carries the mutation in blood DNA. What is the most likely explanation?

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

The answer and the reasoning

D. Germline mosaicism in one parent

A parent may carry the mutation in a proportion of gametes only, so two affected children can be born to unaffected parents. This is why recurrence risk after an apparent new dominant mutation is low but not zero. Reduced penetrance would require the mutation to be present in the parents.

Option by option

  • A. Uniparental disomy in the children

    Uniparental disomy would not explain a dominant point mutation affecting two siblings.

  • B. X-linked recessive inheritance

    X-linked recessive inheritance does not fit a dominant disease affecting both children.

  • C. Reduced penetrance in both parents

    Reduced penetrance would need the mutation in the parents' blood, which was absent.

  • D. Germline mosaicism in one parent (correct)

    Correct. A mutation limited to the gonad can pass to several children.

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, Germline mosaicism in one parent. A parent may carry the mutation in a proportion of gametes only, so two affected children can be born to unaffected parents.

Why is "Uniparental disomy in the children" not the answer?

Uniparental disomy would not explain a dominant point mutation affecting two siblings.

Why is "X-linked recessive inheritance" not the answer?

X-linked recessive inheritance does not fit a dominant disease affecting both children.

Why is "Reduced penetrance in both parents" not the answer?

Reduced penetrance would need the mutation in the parents' blood, which was absent.

What concept does this question test?

It tests Medical genetics: germline mosaicism in Anatomy. This is why recurrence risk after an apparent new dominant mutation is low but not zero. Reduced penetrance would require the mutation to be present in the parents.

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: germline mosaicism?

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.