L16- Huntington Disease and predictive testing

Question 1

Huntington Disease (HD)

Answer 1

Progressive neurodegenerative disorder with motor, cognitive, and psychiatric disturbances - movements – memory – mood

Movement disorder – chorea, dystonia, bradykinesia, swallowing/ choking, dysarthria

Mood – depression, euphoria, apathy, anxiety, aggression, psychotic symptoms

Cognition – loss of executive functioning, rigidity of thought, memory loss, dementia

Question 2

Genetics of HD

Answer 2

Autosomal dominant disorder
Complete penetrance (probability of a gene or genetic trait being expressed)

HTT gene at 4q16.3
The HD mutation = an expansion of CAG repeats ≥ 40 repeats

Question 3

Huntingtin protein

Answer 3

3144 amino acids - widely expressed in different tissues – function unknown.

Abnormal protein – increased number of glutamine amino acids = polyglutamine (polyQ) expansion which alters protein structure and biochemical properties.

Question 4

Anticipation

Answer 4

the onset of a disorder occurs at an earlier age as it is passed from one generation to the next. Often this is associated with an increase in severity of symptoms

• A phenomenon associated with triplet repeat disorders
• Triplet repeat expansions are unstable and may increase (occasionally contract) when passed to the next generation

Question 5

The phenomenon of anticipation is often linked to the gender of the parent…state for HD, myotonic dystrophy and fragile x syndrome

Answer 5

High anticipation risk
-HD: Paternal inheritance (autosomal dominant)

• Myotonic dystrophy: Maternal inheritance (autosomal dominant)
• Fragile X: Maternal inheritance (X-linked)

Question 6

Other diseases where predictive gene testing is possible:

Answer 6

BRCA (familial breast cancer genes)
HNPCC (Hereditary non-polyposis colon cancer)
Myotonic dystrophy

Question 7

HD- What treatments?

Answer 7

Symptomatic treatment only at present

No prevention or cure

Testing does not save lives