Disorders of Nucleotide Expansion and Splicing 1 (Flipped)

Question 1

Myotonia Congenita is also called…and what is mutation

Answer 1

Congenital myotonic dystrophy…voltage-gated ion channel in 1 of 3 ways

1) Potential is shifted
2) Mutated proteins comprising the channels unstable
3) Channel proteins not transported efficiently to cell surface

Question 2

Chloride ion channels responsbile for

Answer 2

Shutting off electrical excitation in the muscles

Question 3

Myotonia congenita causes

Answer 3

Hyperexcitability

Question 4

How is MC different from DM

Answer 4

Mutation are in a chloride channel important for muscle function…in DM this is caused by splicing mutations

Question 5

Myotonic Dystrophy mutation

Answer 5

In DMPK (DM1, chr 19) or ZNF9 (DM2, chr 3) gene

Question 6

Symtpoms of DM 1

Answer 6

Progressive myotonia (because of missplicing of chloride channels)
Cataracts (always in DM1, sometimes in DM2) (caused by six5 mutation in DM1,)
Endocrine problems similar to T2DM because of insulin receptor splicing

Question 7

DM1 and DM2 other names

Answer 7

Steinert dz

Proximal myotonic myopathy

Question 8

Resp muscle involvement/dysphagia and dysarthria DM1 vs. DM2

Answer 8

Yes in DM1, not in DM2

Question 9

Clinical myotonia DM1 vs. DM2

Answer 9

Common in DM1

Question 10

DM 1 muscle groups

Answer 10

Facial, neck, hand, foot

Question 11

DM 2 muscle groups

Answer 11

Lumb girdle

Question 12

Cog dfects DM1 vs 2

Answer 12

Present in 1

Question 13

Limb girdle muscular dystrophy 2a symptoms and enzyme

Answer 13

LGMD primary affects muscles around hips and shoulder
Progressive thigh weakness, winged scap, wide based stance

Calpain 3

Question 14

Calpains are

Answer 14

Heterodimeric cysteine proteases that are calcium dependent and operate at neutral pH

Question 15

Calpain-3 associates with

Answer 15

Molecular spring titin in muscle sarcomere at the M line and senses sarcomere integrity

Question 16

LGMD “trojan horse model”

Answer 16

Damage to titin (normally subjected to hsear forces during contraction), releases calpain03 that degrades damaged titin

Question 17

Mutated calpain-3 problem

Answer 17

Cannot affect titin degradation and prohibits sarcomere repair

Question 18

DMD mutation

Answer 18

On the X chromosome (dystrophin mutation)

Question 19

DMD causes

Answer 19

Pseudohypertrophy - progressive muscle degeneration

Question 20

Dystrophin important for

Answer 20

Sarcolemmal stability by connecting cytoskeleton of muscle fiber to basal lamina

Question 21

Damage to linkage between subsarcolemmal and ECM over time causes

Answer 21

Muscles to become damage over time becauyse htey repeatedly have to contract and relax - necrosis

Question 22

N-terminal of dystrophin binds to

Answer 22

F-actin

Question 23

Symptoms of DMD

Answer 23

Lack of balance 
Hyperlordosis of spine 
Pseudohypertophy 
Loss of ability to walk 
Mental 
Cardiopulmonary

Question 24

Tx of DMD

Answer 24

Corticosteroids, braces, resp support, PT

Question 25

Fragile X syndrome

Answer 25

Autism specturm features…milder in females…x-linked on FMR1 gene of X chromosome

Question 26

FXS repeats

Answer 26

CGG repeats

Question 27

FXS prom characteristics

Answer 27

Interllectual disability, autisum spectrum features, otitis media

Question 28

Physical features of FXS

Answer 28

Elongated face, large/protruding ears, flat feet, enlarged testes, hypotonia

Question 29

How many CGG repeats for diagnosis of FXS

Answer 29

200