Molecular biology and genetics: Friedreich ataxia: 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 · Molecular biology and genetics: Friedreich ataxia

Sample item

A 14-year-old has progressive gait ataxia, absent ankle reflexes, scoliosis, hypertrophic cardiomyopathy and new-onset diabetes. Genetic testing shows an expanded intronic trinucleotide repeat in an autosomal recessive gene. Which protein is deficient?

AAtaxin-1, whose CAG repeat expansion causes cerebellar degenerationBDystrophin, whose loss destabilises the muscle cell membraneCHuntingtin, whose CAG repeat expansion causes toxic gain of functionDFrataxin, needed for mitochondrial iron-sulphur cluster assembly

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

The answer and the reasoning

D. Frataxin, needed for mitochondrial iron-sulphur cluster assembly

Friedreich ataxia is caused by a GAA expansion in the first intron of FXN, which reduces transcription of frataxin. Frataxin is a mitochondrial protein needed for iron-sulphur cluster biogenesis, so deficiency causes mitochondrial iron accumulation and oxidative damage. It is a rare recessive repeat disorder, caused by loss of function.

Option by option

A. Ataxin-1, whose CAG repeat expansion causes cerebellar degeneration
Ataxin-1 is the CAG expansion of dominant spinocerebellar ataxia type 1.
B. Dystrophin, whose loss destabilises the muscle cell membrane
Dystrophin loss causes Duchenne muscular dystrophy, which is X-linked.
C. Huntingtin, whose CAG repeat expansion causes toxic gain of function
Huntingtin involves an exonic CAG expansion and is autosomal dominant.
D. Frataxin, needed for mitochondrial iron-sulphur cluster assembly (correct)
Correct. An intronic GAA expansion silences FXN and lowers frataxin.

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 Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, Frataxin, needed for mitochondrial iron-sulphur cluster assembly. Friedreich ataxia is caused by a GAA expansion in the first intron of FXN, which reduces transcription of frataxin.

Why is "Ataxin-1, whose CAG repeat expansion causes cerebellar degeneration" not the answer?

Ataxin-1 is the CAG expansion of dominant spinocerebellar ataxia type 1.

Why is "Dystrophin, whose loss destabilises the muscle cell membrane" not the answer?

Dystrophin loss causes Duchenne muscular dystrophy, which is X-linked.

Why is "Huntingtin, whose CAG repeat expansion causes toxic gain of function" not the answer?

Huntingtin involves an exonic CAG expansion and is autosomal dominant.

What concept does this question test?

It tests Molecular biology and genetics: Friedreich ataxia in Biochemistry. Frataxin is a mitochondrial protein needed for iron-sulphur cluster biogenesis, so deficiency causes mitochondrial iron accumulation and oxidative damage. It is a rare recessive repeat disorder, caused by loss of function.

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 Molecular biology and genetics: Friedreich ataxia?

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.