HD

Question 1

Genetic mutation in HD

Answer 1

CAG repeats in Exon 1 of HD gene at 4p16.3 where number of repeats surpasses normal threshold

Question 2

Role of anticipation in HD process

Answer 2

Repeated sequences are more likely to be replicated incorrectly due to polymerase slippage, so repeats expand in gamete formation
(More unstable in spermatogenesis than in ooogenesis, so inheriting from dad is usually worse)

More repeats=earlier onset of disease

Question 3

Number of repeats in normal vs HD patients and range for “carriers”

Answer 3

<35= normal

27-35=potential to have offspring with HD

36 or greater=affected

36-39=later onset/reduced penetrance

40 or greater=full penetrance

Question 4

Pathology of HD

Answer 4

Hypothesis that the abnormal protein aggregates to form neural inclusions, which then lead to neurodegeneration (Huntingtin protein highly expressed in neurons)

Question 5

Primary symptoms of HD

Answer 5

Motor function abnormalities- problems with voluntary movement

Cognitive function abnormalities- frontal lobe dysfunction, psychiatric disturbances

Question 6

HD-mode of inheritance

Answer 6

Autosomal dominant (50% RR)

Anticipation typically only occurs when inherited from male

Question 7

Drug targets of HD

Answer 7

• stem cell therapy to correct CAG repeat

- treat symptoms only (psychiatric medications, meds for chorea etc)