Question

Which of the following is a true statement regarding Huntington's chorea?

• A. There is a loss of function type of mutation
• B. It is an autosomal recessive disorder
• C. It is a trinucleotide repeat expansion type of disorder
• D. There is an increased number of CAA repeats

Hint:

Caudate atrophy, autosomal dominant, and an unstable CAG triplet.

Answer 1

The Correct Option is C

Step 1: Huntington's disease (chorea) is caused by expansion of an unstable trinucleotide repeat in the HTT gene, so it is a trinucleotide repeat expansion disorder. Option (c) is correct.
Step 2: The specific repeat is CAG, not CAA, and an increased number of CAG repeats (above about 36 to 40) causes disease, so option (d) is wrong.
Step 3: It is autosomal dominant, not recessive, so option (b) is wrong. The mutation is a gain of function: the expanded polyglutamine huntingtin protein is toxic to neurons, so option (a), loss of function, is wrong.
Clinical: It presents with involuntary jerky (choreiform) movements, mood and behavioral disturbance, and progressive dementia, with anticipation across generations.
Ref: Lange Biochemistry and Genetics Flash Cards, Huntington's Disease, p 161.