Trinucleotide Repeat

Question 1

[Gen/TNR]

Examples of Trinucleotide repeat diseases (6)

Answer 1

1. Fragile X (FMR1)
2. Friedreich ataxia (FXN)
3. Huntington disease (HTT)
4. Myotonic dystrophy (DMPK, CNBP)
5. Spinocerebellar ataxia (ATXN1, FGF14, and SPTBN2)
6. Dentatorubral-pallidoluysian atrophy (ATN1)

Question 2

[Gen/TNR/DM]

Gene, location, trinucleotide repeat for Myotonic dystrophy?

Answer 2

Gene: DMPK gene
Location: 3’ untranslated region of myotonin kinase (DMPK) gene
Repeat: > 50 CTG

Question 3

[Gen/TNR/DM]

Clinical muscular features of myotonic dystrophy? (3)

Answer 3

1. Progressive weakness/wasting
2. Involvement of facial and jaw muscles (ptosis, atrophy of SCM)
3. Distal>Proximal, eg. Difficult to let go of handshake

Question 4

[Gen/TNR/DM]

Organ involved in myotonic dystrophy other than neurologic symptoms? (4)

Answer 4

1. Eye: Cataract
2. Cardiac: Cardiac conduction abnormalities
3. Endo: Testicular atropy, DM
4. Skin: Premature balding

Question 5

[Gen/TNR/FXS]

Site, location and repeat of ‘fragile site’ for Fragile X?

Answer 5

Xq27.3

5’ untranslated
promoter region
upstream of FMR1 gene

Repeat: CGG

Question 6

[Gen/TNR/FXS]

Premutation/Full mutation for Fragile X?

Answer 6

Normal: <55
Premutation 55-200
Full mutation >200

Question 7

[Gen/TNR/FXS]

Male full mutation symptoms for Fragile X (5)

Answer 7

1. Large head/long face
2. Large hands/feet
3. Intellectual disability
4. Macroorchidism after puberty
5. Hyperextensible joints

Question 8

[Gen/TNR/FXS]

Symptoms of female full mutation carrier in Fragile X syndrome? (2)

Answer 8

1. Mild cognitive/behavioral deficits
2. Premature ovarian failure

Question 9

[Gen/TNR/FXS]

Symptoms for fragile X-associated tremor/ataxia syndrome? (3)

Answer 9

1. Intention tremor
2. Gait ataxia
3. Parkinsonism
   (Occurs in >30% of male, >50 of age, progressive neurodegenerative disorder)

Question 10

[Gen/TNR/FA]

Characteristics of Friedreich ataxia? (5)
- Age
- Presentation
- Sensory, Reflex
- Commonly associated disease

Answer 10

1. Age at onset: 10-15 yrs
2. Slowly progressive ataxia
   dysarthria, muscle weakness, spasticity
3. Particularly in the lower limbs, scoliosis, bladder dysfunction
4. Absent lower-limb reflexes, and loss of position and vibration sense
5. Diabetes mellitus

Question 11

[Gen/TNR/FA]

Friedreich ataxia

Inherited pattern?
Genetic cause?

Answer 11

Autosomal recessive
FXN on chromosome 9