Epilepsy Mutations Flashcards
What is a mis-sense mutation?
A change in one amino acid
What is a non-sense mutation?
Change causes a stop codon and truncated protein
What can frame shift do?
change the sequence or cause a stop codon
What happens in y+/- mice?
increase anxiety
What are the degrees of folding?
1
2
3
What are the forms of processing protein folding?
protein glycosylation
disulphide bond formation
protein folding and oligomerisation
What are the chaperone proteins involved with tertiary and quaternary structure folding?
BiP - kinda immature form
Calnexin - most immature form
How are disulphide bonds monitored?
PDI
Where does BiP bind on the protein?
hydrophobic domain
What is the R43Q mutation?
a mutation in receptor biogenesis with y subunit
Which a subunit mutation causes instability?
A322D
What does R43 do?
forms inter-subunit contacts
What is the lack of interaction in R43?
between a1 and b2
b2 and y2
What is the epilepsy mutation?
y2 with b2 interactions cause a problem with receptor conformation
What does dynasor show?
that the mutant receptors are internalised in clatharin coated vesicles
What other mutations show poor assembly?
R82Q and P83S
What is the disturbance caused by the R177G mutation?
incorporation of y2 seems to reduce density and cause subunits to be retained in ER and degraded
What mutation is associated with Dravet syndrome?
Q351X
What are Na channels involved with in epilepsy?
Generalised with febrile seizures in children
B1 in Australian GEFS
What are K channels involved with in epilepsy?
Episodic ataxia - type 1
What are the mutations associated with K channel epilepsy?
missense
What are the different types of channel in K channel epilepsy?
4 inactive
1 slow activating
1 rapid inactivating
What are Ca channels involved in?
Migraine - more females than males
What are symptoms of migraine?
headache
nausea
vomiting
sensitivity to light and noise
