Mutation of the muscle-specific intermediate filament desmin leads to the rare disease desmin-related myopathy. This disorder starts with weakness of the lower limbs when patients are in their 20s or 30s. As symptoms worsen, weakness in respiratory and cardiac muscles occurs, which can lead to serious problems including sudden cardiac arrest. Which of the following mutations would disrupt desmin intermediate filament structure or function and could explain the symptoms of desmin-related myopathy? Choose all of the possible mutations. (A) Mutation such that formation of dimers is blocked. (B) Alteration in the twist or coiling of the dimers, blocking formation of staggered tetramers. (C) Disruption of the polarity of the final desmin strands. (D) Alteration in head groups, so tetramers are unable to link end to end.

(A) Mutation such that formation of dimers is blocked.

(B) Alteration in the twist or coiling of the dimers, blocking formation of staggered tetramers.

(C) Disruption of the polarity of the final desmin strands.

Explanation:

Desmin is an intermediate muscle specific filament protein. It is a very important intermediate filament protein in the smooth muscles skeletal and cardiac muscles.

Desmin related myopathy is disorder that causes mutations in desmin. The effects of this mutation on desmin results in weakness of the muscles of the both the lowered and upper limbs, respiratory failure (problems with breathing), weakness of the cardiac and skeletal muscles as well thereby causing irregular beating of the heart which could result in an heart attack.

The possible mutations that could lead to this desmin related myopathy are:

a. Mutations in desmin such that formation of dimers is blocked.

b. Alteration in the twist or coiling of the dimers, blocking formation of staggered tetramers.

c. Disruption of the polarity of the final desmin strands.