Genetics: cystic fibrosis CFTR mutation: 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 · Genetics: cystic fibrosis CFTR mutation

Sample item

A 2-year-old child with recurrent chest infections and steatorrhoea has a sweat chloride of 90 mmol/L. Genotyping shows homozygosity for the deltaF508 mutation. What is the effect of this mutation on the CFTR protein?

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

The answer and the reasoning

B. Misfolding with retention in the endoplasmic reticulum and degradation, so little reaches the cell surface

DeltaF508 is a 3-base-pair in-frame deletion removing phenylalanine at position 508, the most common CFTR mutation. The abnormal protein misfolds and is degraded by the proteasome after endoplasmic reticulum quality control, so the chloride channel is absent from the apical membrane (a class II defect). CFTR correctors such as elexacaftor and tezacaftor improve its folding and trafficking, and ivacaftor potentiates channel opening.

Option by option

  • A. Complete absence of the CFTR gene on chromosome 7

    The gene is present in deltaF508 homozygotes and carries a small deletion.

  • B. Misfolding with retention in the endoplasmic reticulum and degradation, so little reaches the cell surface (correct)

    Impaired folding and trafficking cause loss of surface channels.

  • C. Production of a normal protein with a defective chloride channel pore

    A channel with a defective pore describes a gating or conductance mutation, not deltaF508.

  • D. Overproduction of CFTR with excessive chloride secretion

    Chloride secretion is reduced in cystic fibrosis, not excessive.

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 B, Misfolding with retention in the endoplasmic reticulum and degradation, so little reaches the cell surface. DeltaF508 is a 3-base-pair in-frame deletion removing phenylalanine at position 508, the most common CFTR mutation.

Why is "Complete absence of the CFTR gene on chromosome 7" not the answer?

The gene is present in deltaF508 homozygotes and carries a small deletion.

Why is "Production of a normal protein with a defective chloride channel pore" not the answer?

A channel with a defective pore describes a gating or conductance mutation, not deltaF508.

Why is "Overproduction of CFTR with excessive chloride secretion" not the answer?

Chloride secretion is reduced in cystic fibrosis, not excessive.

What concept does this question test?

It tests Genetics: cystic fibrosis CFTR mutation in Biochemistry. The abnormal protein misfolds and is degraded by the proteasome after endoplasmic reticulum quality control, so the chloride channel is absent from the apical membrane (a class II defect). CFTR correctors such as elexacaftor and tezacaftor improve its folding and trafficking, and ivacaftor potentiates channel opening.

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 Genetics: cystic fibrosis CFTR mutation?

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.