Epilepsy Mutations

Question 1

What is a mis-sense mutation?

Answer 1

A change in one amino acid

Question 2

What is a non-sense mutation?

Answer 2

Change causes a stop codon and truncated protein

Question 3

What can frame shift do?

Answer 3

change the sequence or cause a stop codon

Question 4

What happens in y+/- mice?

Answer 4

increase anxiety

Question 5

What are the degrees of folding?

Answer 5

1
2
3

Question 6

What are the forms of processing protein folding?

Answer 6

protein glycosylation
disulphide bond formation
protein folding and oligomerisation

Question 7

What are the chaperone proteins involved with tertiary and quaternary structure folding?

Answer 7

BiP - kinda immature form

Calnexin - most immature form

Question 8

How are disulphide bonds monitored?

Answer 8

PDI

Question 9

Where does BiP bind on the protein?

Answer 9

hydrophobic domain

Question 10

What is the R43Q mutation?

Answer 10

a mutation in receptor biogenesis with y subunit

Question 11

Which a subunit mutation causes instability?

Answer 11

A322D

Question 12

What does R43 do?

Answer 12

forms inter-subunit contacts

Question 13

What is the lack of interaction in R43?

Answer 13

between a1 and b2

b2 and y2

Question 14

What is the epilepsy mutation?

Answer 14

y2 with b2 interactions cause a problem with receptor conformation

Question 15

What does dynasor show?

Answer 15

that the mutant receptors are internalised in clatharin coated vesicles

Question 16

What other mutations show poor assembly?

Answer 16

R82Q and P83S

Question 17

What is the disturbance caused by the R177G mutation?

Answer 17

incorporation of y2 seems to reduce density and cause subunits to be retained in ER and degraded

Question 18

What mutation is associated with Dravet syndrome?

Answer 18

Q351X

Question 19

What are Na channels involved with in epilepsy?

Answer 19

Generalised with febrile seizures in children

B1 in Australian GEFS

Question 20

What are K channels involved with in epilepsy?

Answer 20

Episodic ataxia - type 1

Question 21

What are the mutations associated with K channel epilepsy?

Answer 21

missense

Question 22

What are the different types of channel in K channel epilepsy?

Answer 22

4 inactive
1 slow activating
1 rapid inactivating

Question 23

What are Ca channels involved in?

Answer 23

Migraine - more females than males

Question 24

What are symptoms of migraine?

Answer 24

headache
nausea
vomiting
sensitivity to light and noise

Question 25

What is familial hemiplagic migraine?

Answer 25

paralyses to half body
progressive cerebellar atrophy
a1A

Question 26

What is Episodic Ataxia?

Answer 26

intermittent cerebellar ataxia
migrain
cerebellar atrophy
all precipitated by stress

Question 27

What are the mutations with episodic ataxia?

Answer 27

frameshift or substitution

Question 28

What is spinocerebellar ataxia?

Answer 28

slow progressive cerebellar ataxia
nystagmus
proprioceptive sensory loss
severe neuronal loss in cerebellum

Question 29

What are the a1 subunit mouse mutants?

Answer 29

tottering

leaner

Question 30

What are the b subunit mouse mutants?

Answer 30

lethargic mice

Question 31

What are the y subunit mouse mutants?

Answer 31

stargazer mice

Question 32

What is rasmussens encephalitis?

Answer 32

progressive single cerebral epilepsy
severe
hemiplagia
dementia
brain inflammation

Question 33

What is occuring in Rasmussens?

Answer 33

increase AMPAR -> excitotoxicity