Pigmentary disorders: MC1R and pheomelanin: practice question

A Dermatology 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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Dermatology · Pigmentary disorders: MC1R and pheomelanin

Sample item

A man with red hair and fair freckled skin that burns and never tans has a higher lifetime melanoma risk. Which change in melanin synthesis underlies this phenotype?

AShift from eumelanin to pheomelanin through reduced MC1R signallingBFailed melanosome transfer to keratinocytes through LYST defectCShift from pheomelanin to eumelanin through excess MC1R signallingDAbsent tyrosinase activity preventing any melanin synthesis

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

The answer and the reasoning

A. Shift from eumelanin to pheomelanin through reduced MC1R signalling

Loss-of-function variants of MC1R reduce alpha-MSH signalling, so melanocytes make more pheomelanin and less photoprotective eumelanin. This gives red hair, fair skin, freckling and poor tanning, and pheomelanin also generates oxidative damage, raising melanoma risk independent of UV dose.

Option by option

A. Shift from eumelanin to pheomelanin through reduced MC1R signalling (correct)
Correct. Reduced MC1R signalling favours pheomelanin over protective eumelanin.
B. Failed melanosome transfer to keratinocytes through LYST defect
Failed melanosome transfer from a LYST defect belongs to Chediak-Higashi syndrome, with silvery hair and immune defects.
C. Shift from pheomelanin to eumelanin through excess MC1R signalling
Excess MC1R signalling would favour eumelanin, giving darker pigmentation and better tanning.
D. Absent tyrosinase activity preventing any melanin synthesis
Absent tyrosinase is albinism, with white hair and no tanning or freckling at all.

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.

Questions about this Dermatology question

What is the answer to this Dermatology question?

The best answer is A, Shift from eumelanin to pheomelanin through reduced MC1R signalling. Loss-of-function variants of MC1R reduce alpha-MSH signalling, so melanocytes make more pheomelanin and less photoprotective eumelanin.

Why is "Failed melanosome transfer to keratinocytes through LYST defect" not the answer?

Failed melanosome transfer from a LYST defect belongs to Chediak-Higashi syndrome, with silvery hair and immune defects.

Why is "Shift from pheomelanin to eumelanin through excess MC1R signalling" not the answer?

Excess MC1R signalling would favour eumelanin, giving darker pigmentation and better tanning.

Why is "Absent tyrosinase activity preventing any melanin synthesis" not the answer?

Absent tyrosinase is albinism, with white hair and no tanning or freckling at all.

What concept does this question test?

It tests Pigmentary disorders: MC1R and pheomelanin in Dermatology. This gives red hair, fair skin, freckling and poor tanning, and pheomelanin also generates oxidative damage, raising melanoma risk independent of UV dose.

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 Pigmentary disorders: MC1R and pheomelanin?

Learn each condition by its primary lesion, site and signature sign. Then use the flashcards and the other Dermatology 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.