DMD

Question 1

DMD is a

Answer 1

Sex-linked disorder that has almost complete penetrance in males

Question 2

Mutant DMD gene found at position

Answer 2

X21.2-22.1

Question 3

DMD gene is regulated by

Answer 3

Three 5’ promoters and four internal promoters

Question 4

DMD is a rod shaped protein with

Answer 4

4 functional domains that is crucial for stabilisation of the sarcolemma (Muntoni et al., 2003)

Question 5

Hinge region interrupting the 24-spectrin-like repearts in the rod domain provide

Answer 5

elasticity to the protein (Gao et al., 2015)

Question 6

Associated proteins in the cysteine-rich domain and carboxyl-terminus domain allow

Answer 6

Protein to form the dystrophin-associated glycoprotein (DAG) complex

Question 7

DAG complex is vital for

Answer 7

Maintaining muscle integrity

Question 8

Stabilisation is mediated by the DAG complex which directly

Answer 8

Links the basal lamina of the extracellular matrix to the cytoskeleton of the muscle

Question 9

Dystrophin acts as a

Answer 9

Chain that links the skeleton of the myocyte to the extracellular matrix

Question 10

LoF leads to

Answer 10

destabilisation of muscle membrane which results in excess influx of calcium into skeletal and cardiac muscle cells due to hypercontracted muscle fibres and membranes

Question 11

Excessive calcium influx activates proteases within the muscle that..

Answer 11

further potentiates calcium influx causing apoptosis, necrosis and muscle degeneration

Question 12

Mutations in DMD have ..

Answer 12

Pleiotropic effect

affect CV and respiratory systems

Question 13

Initial symptoms of patients with DMD are

Answer 13

Waddling gait and difficulty climbing stairs (evident between 2-5 years of age)
delayed developmental milestones (Blake et al., 2002)
and Gower’s sign

Question 14

Gower’s sign

Answer 14

child uses arms to climb up their body in order to assume standing position from laying down
characterised by pelvic girdle weakness

Question 15

Elevated levels of creatine kinase in blood serum which is produced in

Answer 15

damaged muscle

Question 16

over 4000 mutations in DMD have been found

Answer 16

Blake et al 2002

Question 17

Intragenic deletions account for

Answer 17

60-65% of mutations causing DMD (Tayeb 2010)

Question 18

Exonic deletions can occur

Answer 18

anywhere in the gene

Question 19

Mutational hotspots at

Answer 19

5’ end of the gene and in the distal region

Gao 2015

Question 20

Result of LoF of dystrophin protein and severity of disease is dependent on..

Answer 20

how the mutations affect the reading frame of the protein

Question 21

More than 90% of deletion mutations in DMD

Answer 21

disrupt the reading frame of the protein causing a frame-shift

Question 22

Frame-shift causes

Answer 22

Generation of a stop codon ending translation resulting in a truncated and unstable protein and in some cases dystrophin is not produced
(Gao and McNally, 2015)