Muscular Dystrophy

Question 1

Collagen 1 formation

Answer 1

Triple helix formed in the cell driven by the c terminal non collagenous domain (don’t have the motif)

Hydroxylation of the proline and lysine happened often

Cleavage of non collagenous domains

Question 2

Vitamin C

Answer 2

Co factor for proline hydroxylase

Succinctness is formed from oxogluterate

Question 3

Types of basal membrane

Answer 3

Stroma unorganised and 3D

Tendon organised and linear

Basal membrane 2D sheet

Question 4

Type 4. Collagen

Answer 4

Basement membrane only

The non collagenous domains are not cleaved as with type 1

Forms in flat membranes non helical

N terminus forms disulphides bonds between 4 triple helices

C terminus forms end interactions to create hexamers

Question 5

Combinations of collagen 4

Answer 5

112
345
556

Question 6

Alports syndrome

Most common form?

Answer 6

Wrong type collagen 4 formation in the kidney as there is only 112 where as 345 is required to protect the kidney basement membranes from the internal pressure as it has more cross links than type 112

Most common is X linked 4a5 never in female

autosomal recessive associated with collagen 4a4 and 4a3

Question 7

Mutations in…

Early onset

Late onset

Answer 7

Nonsense mutations leading to trucations

Missense leading to conserved cysteine residues affecting crosslinking

Question 8

Good pastures syndrome

Answer 8

Same as alports but with progressive glomerulonepritis (filter damage)

Question 9

ACE inhibitors

Answer 9

Reduce onset of alports

Induces vasodilation reducing damage and pressure to the glomerulus

Question 10

Laminin structure

Answer 10

Three chains

Alpha beta gamma

Chains interact and from a triple helices structure with a globular domain on the C terminus of the alpha chain whilst the N terminus has spacers comprised of EGF repeats at the globular domain

Specific repeating structure forming disulphides bonds at the cross links

Question 11

Piersons syndrome

Answer 11

Renal disease in eye abnormalities and severe muscular hypontia

Mutation in b2 integrity gene in laminin 11

Question 12

Epidermolysis bullosa

Answer 12

Laminin 5 mutation cause breaks between the dermal epidermal junction

Loss of 5 causes causes herlitz type

Links structures called hemidesmosomes

Question 13

Therapies for beta 3 laminin mutations

Answer 13

Transplantation of epidermal cells after retrovirus transduction into the stem cells

Question 14

Integrins

Answer 14

Heterodimers single transmembrane domain and short cytoplasmic domain but not beta4

Cytoplasmic domain interacts with cytoskeleton such as actin or keratin

Question 15

Beta 4 integrin deletion

Answer 15

Results in the loss of hemidesmosomes but not cell cell adhesions

Question 16

Loss of beta 4

Answer 16

Results in absence of alpha 6 subunit

Question 17

Pyloric atresia

Answer 17

Miss sense mutation in alpha 6 leading to rapid degradation of the integrin autosomal recessive

Question 18

Eb simplex

Answer 18

Tearing of the epidermis from the basement membrane attachment

Question 19

Congenital muscular dystrophy

Answer 19

Alpha 2 laminin mutation

Progressive degeneration of muscles

Laminin 211 main muscle BM laminin binding the integrin on the muscle cell surface

Question 20

Loss of alpha 7 integrin

Answer 20

Results in progressive muscular dystrophy

Question 21

Duschenne muscular dystrophy

Answer 21

X linked

Mutated dystrophin independent on 71 integrin attachment

Complete loss of dystrophin

Question 22

Becker MD

Answer 22

Partially functional dystrophin

Question 23

Dystroglycan glycoprotein complex

Answer 23

Links actin and muscle BM however if both are lost the MD is much worse than the loss of just one

Question 24

Laminin Dystroglycan binding

Answer 24

Laminin 211 binds glycosylated moieties on dystroglycan however if the Olinked sugars on dystroglycan are removed them laminin cannot bind.

Question 25

Fukuyama CMD

Answer 25

Autosomal recessive involved in glycosylation of alpha dystroglycan

That doesn’t happen so laminin cannot bind

Question 26

Disruption of alpha 7 or dystroglycan binding laminin 2

Answer 26

Causes muscle cell apoptosis as akt is activated causing bax to trigger it

Question 27

Collagen structure definied

Answer 27

Triple helix with

Gly X Y motif

Question 28

Laminin 1

Answer 28

Embryonic lethal

Question 29

Laminin 2

Answer 29

Muscular dystrophy

Question 30

Laminin 5

Answer 30

Epidermolysis bullosa

Question 31

Integrin b4

Answer 31

Epidermolysis bullosa

Question 32

B2 integrin

Answer 32

Leukocyte adhesion disorder