Collagen disorders: osteogenesis imperfecta: 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 · Collagen disorders: osteogenesis imperfecta

Sample item

A newborn has multiple intrauterine fractures, blue sclerae and deformed long bones. Sequencing shows a heterozygous COL1A1 variant replacing a glycine in a Gly-X-Y repeat with a bulky amino acid. What is the main molecular effect?

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

The answer and the reasoning

C. The mutant chain disrupts triple helix folding and also impairs the normal chains (dominant negative effect)

Glycine, the smallest amino acid, must occupy every third position so that three chains can pack tightly into a triple helix. A bulky substitute causes steric hindrance, delays folding and produces unstable collagen; because mutant chains incorporate into trimers with normal ones, the effect is dominant negative. This explains the severe type II or III osteogenesis imperfecta.

Option by option

  • A. Failure to cleave the amino-terminal propeptide of procollagen, causing fragile skin

    A propeptidase defect causes dermatosparaxis-type Ehlers-Danlos syndrome with skin fragility, not fractures with blue sclerae.

  • B. Failure of lysyl oxidase to cross-link collagen fibrils because of copper deficiency

    Impaired cross-linking from lysyl oxidase failure is seen in copper deficiency and Menkes disease, not a COL1A1 sequence change.

  • C. The mutant chain disrupts triple helix folding and also impairs the normal chains (dominant negative effect) (correct)

    A glycine substitution disrupts helix formation and poisons trimers containing even one mutant chain.

  • D. Lack of prolyl hydroxylation of procollagen chains because of vitamin C deficiency

    Defective prolyl hydroxylation is the mechanism of scurvy, and no vitamin deficiency is present here.

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 mutant chain disrupts triple helix folding and also impairs the normal chains (dominant negative effect). Glycine, the smallest amino acid, must occupy every third position so that three chains can pack tightly into a triple helix.

Why is "Failure to cleave the amino-terminal propeptide of procollagen, causi…" not the answer?

A propeptidase defect causes dermatosparaxis-type Ehlers-Danlos syndrome with skin fragility, not fractures with blue sclerae.

Why is "Failure of lysyl oxidase to cross-link collagen fibrils because of co…" not the answer?

Impaired cross-linking from lysyl oxidase failure is seen in copper deficiency and Menkes disease, not a COL1A1 sequence change.

Why is "Lack of prolyl hydroxylation of procollagen chains because of vitamin…" not the answer?

Defective prolyl hydroxylation is the mechanism of scurvy, and no vitamin deficiency is present here.

What concept does this question test?

It tests Collagen disorders: osteogenesis imperfecta in Biochemistry. A bulky substitute causes steric hindrance, delays folding and produces unstable collagen; because mutant chains incorporate into trimers with normal ones, the effect is dominant negative. This explains the severe type II or III osteogenesis imperfecta.

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 Collagen disorders: osteogenesis imperfecta?

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.