HD / MYD

Question 1

Repeat sizes of myotonic dystrophy

Answer 1

Unaffected: <50 repeats
Mild: 50-150 repeats
Classical DM1: 100-1000 repeats (onset 10-30)
Congenital: Severe, >1000 repeats (onset from birth to 10yrs)

Question 2

Huntington’s repeat sizes

Answer 2

Unaffected: <26
Intermediate: 27-35
Reduced penetrance: 36-39
Affected: 40+
Juvenile: 60+ (usually)

Question 3

How does nusinersen work?

Answer 3

Antisense oligonucleotide
Binds pre-mRNA SMN2
Prevents spice repressor binding
Enables more full length SMN protein to be made
Enables inclusion of SMN2 exon 7

Question 4

Features of Myotonic dystrophy

Answer 4

Trinucleotide repeat expansion of CTGs in DMPK gene
Associated with systemic abnormalities
Skeletal and smooth muscle weakness
abnormalities of eyes, heart and endocrine system
learning disabilities

Question 5

Huntington’s disease features

Answer 5

*Mood swings (mood disorder)
*Cognitive decline
Decline in mood, behaviour
*Clumsiness
*Chorea like movements (hand shaking)

Question 6

SMA features

Answer 6

Type 1: Hypotonia (onset from birth)
Type 2: onset within 6 months (cannot sit unaided)
Type 3: Can sit, but perhaps cannot walk
Type 4: May be able to walk, onset later in life, may loose the ability to walk

Question 7

Huntington’s repeat of:

Answer 7

CAG repeat in HTT gene

Question 8

Myotonic dystrophy repeat of:

Answer 8

CTG in DMPK gene

Question 9

Explain SMA Bayes

Answer 9

• Risk calculation
• Uses series of formulas based on prior risk that a patient is a carrier vs non carrier (based on percentage chance of inheriting a high risk allele from a parent)
• Takes into consideration a number of conditional statistics (eg. Frequency of 2 copies of SMN1 on 1 chromosome, is different in different populations)
• Joint Risk (combines risks of prior risk and conditional)
• Final risk: uses formula taking all of this information into account to generate a residual risk of being a carrier