TNR Disorders

Question 1

Genetic anticipation

Answer 1

Through generations, disease presents @ earlier age and with greater severity

Question 2

In HD, how many repeats to be affected?

Answer 2

> 39

Question 3

HD expansion transmitted primarily by?

Answer 3

Father

Question 4

Where is the TNR for HD?

Answer 4

Coding region (Exon 1)

Question 5

3 phenotypes of huntingtons

Answer 5

Neurodegenerative chorea, behavior changes, dementia

Question 6

Mechanism of HD

Answer 6

Misfolded protein aggregates from extra glutamines causes cell dysfunction

Question 7

Fragile X Syndrome - TNR location?

Answer 7

5’ UTR

Question 8

Fragile X Syndrome - # repeats for normal, PM, FM?

Answer 8

Normal - 200

Question 9

Fragile X Syndrome - Mechanism of PM disease?

Answer 9

PM - RNA toxicity

Question 10

Fragile X Syndrome - Mechanism of FM disease?

Answer 10

Promoter methylation; no FMR protein

Question 11

What is function of FMR protein?

Answer 11

It is an RNA - Binding protein, brings in RISC, acts as translational regulator

Question 12

Fragile X Syndrome - Type of inheritance?

Answer 12

XLR

Question 13

Fragile X Syndrome - PM phenotype (2)

Answer 13

Premature ovarian failure before 40

Tremor ataxia

Question 14

Fragile X Syndrome - FM phenotype (4)

Answer 14

Severe cognitive defect, autism, altered facies, large testes

Question 15

Fragile X Syndrome - affects males or females primarily?

Answer 15

Males (XLR)

Question 16

Friedrich’s ataxia - full mutation repeats?

Answer 16

> 200

Question 17

Friedrich’s ataxia - TNR location?

Answer 17

1st intron (no splicing, RNA gets degraded)

Question 18

Friedrich’s ataxia - Mechanism of disease?

Answer 18

MRNA transcript degredation, loss of frataxin protein, mitochondrial dysfunction.

Question 19

Friedrich’s ataxia - Clinical phenotype

Answer 19

Hereditary ataxia (neurologic dysfunction), cardiomyopathy, diabetes mellitus

(Heart, brain, pancreatic beta cells)

Question 20

Myotonic Dystrophy 1 - TNR locationn

Answer 20

3’ UTR

Question 21

Myotonic Dystrophy 1 - inheritance pattern

Answer 21

AD

Question 22

Myotonic Dystrophy 1 - mild, moderate, severe repeats

Answer 22

Mild 50-150,
Moderate 100-1000
Severe >1,000

Question 23

Expansion transmission of Myotonic Dystrophy 1 -

Answer 23

Expansion of >1,000 only from mother, expansion in oocyte.

Question 24

Myotonic Dystrophy 1 - Mechanism of disease

Answer 24

Sequestering of RNA splicing proteins

Question 25

Myotonic Dystrophy 1 - clinical phenotype

Answer 25

Adult onset muscle weakness and wasting, cataracts, arrythmias, NO COGNITIVE IMPAIRMENT