DNA repair: Fanconi anaemia: 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 · DNA repair: Fanconi anaemia

Sample item

A 5-year-old boy has short stature, café-au-lait macules, hypoplastic thumbs and a progressive pancytopenia. Which laboratory result would best confirm the diagnosis and reflect its underlying defect?

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

The answer and the reasoning

A. Increased chromosome breakage with mitomycin C or diepoxybutane, reflecting defective crosslink repair

Fanconi anaemia is caused by mutation in the FANC gene network that repairs DNA interstrand crosslinks. Cells show spontaneous and crosslinker-induced chromosome breaks, radial figures, and the diagnostic test is breakage with diepoxybutane or mitomycin C. Patients develop marrow failure and have high risk of acute myeloid leukaemia and squamous cancers.

Option by option

  • A. Increased chromosome breakage with mitomycin C or diepoxybutane, reflecting defective crosslink repair (correct)

    Crosslinker-induced breakage is the diagnostic test for the interstrand crosslink repair defect.

  • B. Microsatellite instability in tissue samples, reflecting defective mismatch repair

    Microsatellite instability indicates Lynch syndrome and is not seen in this childhood marrow failure syndrome.

  • C. Increased sister chromatid exchanges, reflecting a defective BLM helicase enzyme

    Raised sister chromatid exchange is the hallmark of Bloom syndrome, which presents with short stature and a sun-sensitive facial rash.

  • D. Extreme sensitivity to ultraviolet light in cultured cells, reflecting defective excision repair

    UV hypersensitivity indicates xeroderma pigmentosum, which does not cause marrow failure or thumb anomalies.

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 A, Increased chromosome breakage with mitomycin C or diepoxybutane, reflecting defective crosslink repair. Fanconi anaemia is caused by mutation in the FANC gene network that repairs DNA interstrand crosslinks.

Why is "Microsatellite instability in tissue samples, reflecting defective mi…" not the answer?

Microsatellite instability indicates Lynch syndrome and is not seen in this childhood marrow failure syndrome.

Why is "Increased sister chromatid exchanges, reflecting a defective BLM heli…" not the answer?

Raised sister chromatid exchange is the hallmark of Bloom syndrome, which presents with short stature and a sun-sensitive facial rash.

Why is "Extreme sensitivity to ultraviolet light in cultured cells, reflectin…" not the answer?

UV hypersensitivity indicates xeroderma pigmentosum, which does not cause marrow failure or thumb anomalies.

What concept does this question test?

It tests DNA repair: Fanconi anaemia in Biochemistry. Cells show spontaneous and crosslinker-induced chromosome breaks, radial figures, and the diagnostic test is breakage with diepoxybutane or mitomycin C. Patients develop marrow failure and have high risk of acute myeloid leukaemia and squamous cancers.

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 DNA repair: Fanconi anaemia?

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.